diff --git a/.pre-commit-config.yaml b/.pre-commit-config.yaml
index cbc9aa6d335..42712bb3ac5 100644
--- a/.pre-commit-config.yaml
+++ b/.pre-commit-config.yaml
@@ -74,15 +74,15 @@ repos:
   rev: 24.2.0
   hooks: # check conformance to black formatting
    - id: black
-     #args: ['--diff', '-v', '--target-version', 'py39' ] # if run without arguments, will fail and will format the files
-     args: ['--target-version', 'py39' ] # Allow black to fail and provide auto-formatting to files that need it for compliance
+     #args: ['--diff', '-v', '--target-version', 'py310' ] # if run without arguments, will fail and will format the files
+     args: ['--target-version', 'py310' ] # Allow black to fail and provide auto-formatting to files that need it for compliance
      exclude: ".*build.*|\\/ThirdParty\\/|\\/Data\\/"
 -   repo: https://github.com/asottile/pyupgrade
     rev: v3.19.0
     hooks:
     -   id: pyupgrade
         exclude: ".*build.*|\\/ThirdParty\\/|\\/Data\\/"
-        args: [--py39-plus]
+        args: [--py310-plus]
 - repo: https://github.com/SimpleITK/CommentSpellCheck.git
   rev: v0.4.4
   hooks:
diff --git a/Documentation/docs/contributing/python_packaging.md b/Documentation/docs/contributing/python_packaging.md
index af742232aca..b29a54f5fc5 100644
--- a/Documentation/docs/contributing/python_packaging.md
+++ b/Documentation/docs/contributing/python_packaging.md
@@ -20,7 +20,7 @@ Building ITK Python wheels requires the following:
 - CMake >= 3.16
 - Git
 - C++ Compiler (see [scikit-build platform specific requirements](https://scikit-build.readthedocs.io/en/latest/generators.html))
-- Python >= 3.9
+- Python >= 3.10
 
 ## Automated Platform Scripts
 
@@ -40,11 +40,11 @@ git clone https://github.com/InsightSoftwareConsortium/ITKPythonPackage.git
 
 pushd ITKPythonPackage
 export MANYLINUX_VERSION=2014
-./scripts/dockcross-manylinux-build-wheels.sh cp38
+./scripts/dockcross-manylinux-build-wheels.sh cp310
 [...]
 
 ls -1 dist/
-itk-5.3.0.dev20231108-cp38-cp38m-manylinux2014_x86_64.whl
+itk-6.0.0.dev20260401-cp310-cp310-manylinux2014_x86_64.whl
 ```
 
 ### macOS
@@ -61,11 +61,11 @@ Then, run [macpython-build-wheels.sh](https://github.com/InsightSoftwareConsorti
 git clone https://github.com/InsightSoftwareConsortium/ITKPythonPackage.git
 [...]
 
-./scripts/macpython-build-wheels.sh cp38
+./scripts/macpython-build-wheels.sh cp310
 [...]
 
 ls -1 dist/
-itk-5.3.0.dev20231108-cp38-cp38m-macosx_10_9_x86_64.whl
+itk-6.0.0.dev20260401-cp310-cp310-macosx_11_0_arm64.whl
 ```
 
 ### Windows
diff --git a/Testing/ContinuousIntegration/AzurePipelinesLinux.yml b/Testing/ContinuousIntegration/AzurePipelinesLinux.yml
index 7d56c2727cd..72912b467ee 100644
--- a/Testing/ContinuousIntegration/AzurePipelinesLinux.yml
+++ b/Testing/ContinuousIntegration/AzurePipelinesLinux.yml
@@ -245,7 +245,7 @@ jobs:
       displayName: "Checkout pull request HEAD"
     - task: UsePythonVersion@0
       inputs:
-        versionSpec: "3.9"
+        versionSpec: "3.10"
         architecture: "x64"
     - bash: |
         set -x
diff --git a/Wrapping/Generators/Python/CMakeLists.txt b/Wrapping/Generators/Python/CMakeLists.txt
index b4f0cefb7f3..dd496c2a010 100644
--- a/Wrapping/Generators/Python/CMakeLists.txt
+++ b/Wrapping/Generators/Python/CMakeLists.txt
@@ -166,7 +166,7 @@ if(NOT EXTERNAL_WRAP_ITK_PROJECT)
   )
 
   configure_file(
-    "${CMAKE_CURRENT_SOURCE_DIR}/itkConfig.py.in"
+    "${CMAKE_CURRENT_SOURCE_DIR}/itkConfig.template.in.py"
     "${ITK_WRAP_PYTHON_ROOT_BINARY_DIR}/itkConfig.py"
     @ONLY
   )
diff --git a/Wrapping/Generators/Python/PyBase/pyBase.i b/Wrapping/Generators/Python/PyBase/pyBase.i
index 1f825de6434..c90d8020de7 100644
--- a/Wrapping/Generators/Python/PyBase/pyBase.i
+++ b/Wrapping/Generators/Python/PyBase/pyBase.i
@@ -12,8 +12,8 @@ import collections
 from sys import version_info as _version_info
 # Set values below to the same value as
 # PYTHON_VERSION_MIN in ITKSetPython3Vars.cmake
-if _version_info < (3, 9, 0):
-    raise RuntimeError("Python 3.9 or later required")
+if _version_info < (3, 10, 0):
+    raise RuntimeError("Python 3.10 or later required")
 
 from . import _ITKCommonPython
 %}
diff --git a/Wrapping/Generators/Python/itk/pyi_generator.py b/Wrapping/Generators/Python/itk/pyi_generator.py
index 3b4ee8d99ff..d8007fb6aed 100644
--- a/Wrapping/Generators/Python/itk/pyi_generator.py
+++ b/Wrapping/Generators/Python/itk/pyi_generator.py
@@ -10,7 +10,6 @@
 from io import StringIO
 from pathlib import Path, PurePath
 import pickle
-from typing import Union
 import glob
 import re
 from collections import defaultdict
@@ -380,7 +379,7 @@ def write_class_proxy_pyi(
         pyi_file.write(interfaces_code)
 
 
-def unpack(file_names: [str], save_dir: str) -> Union[str, None]:
+def unpack(file_names: [str], save_dir: str) -> str | None:
     class_definitions = []
 
     for file_name in file_names:
@@ -429,7 +428,7 @@ def unpack(file_names: [str], save_dir: str) -> Union[str, None]:
         return None
 
 
-def merge(class_definitions: []) -> Union[ITKClass, None]:
+def merge(class_definitions: []) -> ITKClass | None:
     # Merge all the class files together to return one complete class.
     if len(class_definitions) == 0:
         return None
diff --git a/Wrapping/Generators/Python/itk/support/base.py b/Wrapping/Generators/Python/itk/support/base.py
index 33563d5bf95..1d3ce9f08c6 100644
--- a/Wrapping/Generators/Python/itk/support/base.py
+++ b/Wrapping/Generators/Python/itk/support/base.py
@@ -21,7 +21,7 @@
 from sys import stderr as system_error_stream
 
 # Required to work around weird import error with xarray
-from typing import Any, Optional, Union
+from typing import Any
 from collections.abc import Sequence
 
 import itkConfig
@@ -305,7 +305,7 @@ class ITKTemplateFeatures:
     ('Image',       'itk::Image',   'itkImageSS2',   True,            'signed short,2'),
     """
 
-    def __init__(self, feature_tuple: Sequence[Union[str, bool]]) -> None:
+    def __init__(self, feature_tuple: Sequence[str | bool]) -> None:
         feature_length: int = len(feature_tuple)
         # ITK classes have exactly 5 elements in the tuple, otherwise they are swig classes
         self._is_itk_class: bool = feature_length == 5
@@ -317,7 +317,7 @@ def __init__(self, feature_tuple: Sequence[Union[str, bool]]) -> None:
         self._cpp_class_name: str = feature_tuple[1]
         self._swig_class_name: str = feature_tuple[2]
         self._class_in_module: bool = feature_tuple[3] if feature_length >= 4 else False
-        self._template_parameters: Optional[str] = (
+        self._template_parameters: str | None = (
             feature_tuple[4] if feature_length == 5 else None
         )
 
diff --git a/Wrapping/Generators/Python/itk/support/build_options.py b/Wrapping/Generators/Python/itk/support/build_options.py
index 7744e62a26d..3b9aabee70b 100644
--- a/Wrapping/Generators/Python/itk/support/build_options.py
+++ b/Wrapping/Generators/Python/itk/support/build_options.py
@@ -8,7 +8,6 @@
 from itk.support import types
 from itk.support.template_class import itkTemplate, itkTemplateBase
 
-from typing import Union
 from itkConfig import ITK_GLOBAL_WRAPPING_BUILD_OPTIONS as _itkwrapbo
 
 DIMS: list[int] = [int(s) for s in _itkwrapbo["ITK_WRAP_IMAGE_DIMS"] if s]
@@ -62,7 +61,7 @@
 SCALARS: list[types.itkCType] = INTS + REALS
 VECTORS: list[itkTemplate] = VECTOR_REALS + COV_VECTOR_REALS
 COLORS: list[itkTemplate] = RGBS + RGBAS
-ALL_TYPES: list[Union[types.itkCType, itkTemplate]] = (
+ALL_TYPES: list[types.itkCType | itkTemplate] = (
     COLORS + VECTORS + SCALARS + COMPLEX_REALS
 )
 
diff --git a/Wrapping/Generators/Python/itk/support/extras.py b/Wrapping/Generators/Python/itk/support/extras.py
index 787a0eb85f4..a01f9a3f3b9 100644
--- a/Wrapping/Generators/Python/itk/support/extras.py
+++ b/Wrapping/Generators/Python/itk/support/extras.py
@@ -16,9 +16,11 @@
 #
 # ==========================================================================
 
+from __future__ import annotations
+
 import enum
 import re
-from typing import Optional, Union, Any, TYPE_CHECKING
+from typing import Any, TYPE_CHECKING
 from collections.abc import Sequence
 from sys import stderr as system_error_stream
 
@@ -33,7 +35,7 @@
 import os
 import builtins
 
-fileiotype = Union[str, bytes, os.PathLike]
+fileiotype = str | bytes | os.PathLike
 
 import itk.support.types as itkt
 
@@ -178,7 +180,7 @@ def echo(obj, f=system_error_stream) -> None:
     print(f, obj)
 
 
-def size(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[int]:
+def size(image_or_filter: itkt.ImageOrImageSource) -> Sequence[int]:
     """Return the size of an image, or of the output image of a filter
 
     This method take care of updating the needed information
@@ -192,7 +194,7 @@ def size(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[int]:
     return img.GetLargestPossibleRegion().GetSize()
 
 
-def physical_size(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[float]:
+def physical_size(image_or_filter: itkt.ImageOrImageSource) -> Sequence[float]:
     """Return the physical size of an image, or of the output image of a filter
 
     This method take care of updating the needed information
@@ -208,7 +210,7 @@ def physical_size(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[float]
     return result
 
 
-def spacing(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[float]:
+def spacing(image_or_filter: itkt.ImageOrImageSource) -> Sequence[float]:
     """Return the spacing of an image, or of the output image of a filter
 
     This method take care of updating the needed information
@@ -221,7 +223,7 @@ def spacing(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[float]:
     return img.GetSpacing()
 
 
-def origin(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[float]:
+def origin(image_or_filter: itkt.ImageOrImageSource) -> Sequence[float]:
     """Return the origin of an image, or of the output image of a filter
 
     This method take care of updating the needed information
@@ -234,7 +236,7 @@ def origin(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[float]:
     return img.GetOrigin()
 
 
-def index(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[int]:
+def index(image_or_filter: itkt.ImageOrImageSource) -> Sequence[int]:
     """Return the index of an image, or of the output image of a filter
 
     This method take care of updating the needed information
@@ -247,7 +249,7 @@ def index(image_or_filter: "itkt.ImageOrImageSource") -> Sequence[int]:
     return img.GetLargestPossibleRegion().GetIndex()
 
 
-def region(image_or_filter: "itkt.ImageOrImageSource") -> "itkt.ImageRegion":
+def region(image_or_filter: itkt.ImageOrImageSource) -> itkt.ImageRegion:
     """Return the region of an image, or of the output image of a filter
 
     This method take care of updating the needed information
@@ -318,7 +320,7 @@ def _GetArrayFromImage(
 
 
 def GetArrayFromImage(
-    image_or_filter: "itkt.ImageOrImageSource",
+    image_or_filter: itkt.ImageOrImageSource,
     keep_axes: bool = False,
     update: bool = True,
     ttype=None,
@@ -341,7 +343,7 @@ def GetArrayFromImage(
 
 
 def GetArrayViewFromImage(
-    image_or_filter: "itkt.ImageOrImageSource",
+    image_or_filter: itkt.ImageOrImageSource,
     keep_axes: bool = False,
     update: bool = True,
     ttype=None,
@@ -426,7 +428,7 @@ def _GetImageFromArray(
 
 def GetImageFromArray(
     arr: ArrayLike, is_vector: bool = False, ttype=None
-) -> "itkt.ImageBase":
+) -> itkt.ImageBase:
     """Get an ITK image from a Python array.
 
     This is a deep copy of the NumPy array buffer and is completely safe without potential
@@ -455,7 +457,7 @@ def GetImageFromArray(
 
 def GetImageViewFromArray(
     arr: ArrayLike, is_vector: bool = False, ttype=None, need_contiguous=True
-) -> "itkt.ImageBase":
+) -> itkt.ImageBase:
     """Get an ITK image view (shared pixel buffer memory) from a Python array.
 
     If is_vector is True, then a 3D array will be treated as a 2D vector image,
@@ -484,7 +486,7 @@ def GetImageViewFromArray(
 
 
 def array_from_vector_container(
-    container: "itkt.VectorContainer", ttype=None
+    container: itkt.VectorContainer, ttype=None
 ) -> np.ndarray:
     """Get an Array with the content of the vector container"""
     import itk
@@ -510,7 +512,7 @@ def array_from_vector_container(
 
 
 def array_view_from_vector_container(
-    container: "itkt.VectorContainer", ttype=None
+    container: itkt.VectorContainer, ttype=None
 ) -> np.ndarray:
     """Get an Array view with the content of the vector container"""
     import itk
@@ -535,7 +537,7 @@ def array_view_from_vector_container(
     return itk.PyVectorContainer[keys[0]].array_view_from_vector_container(container)
 
 
-def vector_container_from_array(arr: ArrayLike, ttype=None) -> "itkt.VectorContainer":
+def vector_container_from_array(arr: ArrayLike, ttype=None) -> itkt.VectorContainer:
     """Get a vector container from a Python array"""
     import itk
 
@@ -667,7 +669,7 @@ def GetArrayFromMatrix(itk_matrix) -> np.ndarray:
 array_from_matrix = GetArrayFromMatrix
 
 
-def GetMatrixFromArray(arr: ArrayLike) -> "itkt.Matrix":
+def GetMatrixFromArray(arr: ArrayLike) -> itkt.Matrix:
     import itk
 
     # Verify inputs
@@ -685,7 +687,7 @@ def GetMatrixFromArray(arr: ArrayLike) -> "itkt.Matrix":
 matrix_from_array = GetMatrixFromArray
 
 
-def vtk_image_from_image(l_image: "itkt.ImageOrImageSource") -> "vtk.vtkImageData":
+def vtk_image_from_image(l_image: itkt.ImageOrImageSource) -> vtk.vtkImageData:
     """Convert an itk.Image to a vtk.vtkImageData."""
     import itk
     import vtk
@@ -742,7 +744,7 @@ def vtk_image_from_image(l_image: "itkt.ImageOrImageSource") -> "vtk.vtkImageDat
     return vtk_image
 
 
-def image_from_vtk_image(vtk_image: "vtk.vtkImageData") -> "itkt.ImageBase":
+def image_from_vtk_image(vtk_image: vtk.vtkImageData) -> itkt.ImageBase:
     """Convert a vtk.vtkImageData to an itk.Image."""
     import itk
     from vtk.util.numpy_support import vtk_to_numpy
@@ -788,7 +790,7 @@ def image_from_vtk_image(vtk_image: "vtk.vtkImageData") -> "itkt.ImageBase":
     return l_image
 
 
-def dict_from_image(image: "itkt.Image") -> dict:
+def dict_from_image(image: itkt.Image) -> dict:
     """Serialize a Python itk.Image object to a pickable Python dictionary."""
     import itk
 
@@ -811,7 +813,7 @@ def dict_from_image(image: "itkt.Image") -> dict:
     )
 
 
-def image_from_dict(image_dict: dict) -> "itkt.Image":
+def image_from_dict(image_dict: dict) -> itkt.Image:
     """Deserialize an dictionary representing an itk.Image object."""
     import itk
 
@@ -840,7 +842,7 @@ def image_from_dict(image_dict: dict) -> "itkt.Image":
     return image
 
 
-def mesh_from_dict(mesh_dict: dict) -> "itkt.Mesh":
+def mesh_from_dict(mesh_dict: dict) -> itkt.Mesh:
     """Deserialize an dictionary representing an itk.Mesh object."""
     import itk
 
@@ -868,7 +870,7 @@ def mesh_from_dict(mesh_dict: dict) -> "itkt.Mesh":
     return mesh
 
 
-def dict_from_mesh(mesh: "itkt.Mesh") -> dict:
+def dict_from_mesh(mesh: itkt.Mesh) -> dict:
     """Serialize a Python itk.Mesh object to a pickable Python dictionary."""
     import itk
 
@@ -936,7 +938,7 @@ def dict_from_mesh(mesh: "itkt.Mesh") -> dict:
     )
 
 
-def pointset_from_dict(pointset_dict: dict) -> "itkt.PointSet":
+def pointset_from_dict(pointset_dict: dict) -> itkt.PointSet:
     """Deserialize an dictionary representing an itk.PointSet object."""
     import itk
 
@@ -955,7 +957,7 @@ def pointset_from_dict(pointset_dict: dict) -> "itkt.PointSet":
     return mesh
 
 
-def dict_from_pointset(pointset: "itkt.PointSet") -> dict:
+def dict_from_pointset(pointset: itkt.PointSet) -> dict:
     """Serialize a Python itk.PointSet object to a pickable Python dictionary."""
     import itk
 
@@ -1000,7 +1002,7 @@ def dict_from_pointset(pointset: "itkt.PointSet") -> dict:
     )
 
 
-def polyline_from_dict(polyline_dict: dict) -> "itkt.PolylineParametricPath":
+def polyline_from_dict(polyline_dict: dict) -> itkt.PolylineParametricPath:
     """Deserialize an dictionary representing an itk.PolylineParametricPath object."""
     import itk
 
@@ -1014,7 +1016,7 @@ def polyline_from_dict(polyline_dict: dict) -> "itkt.PolylineParametricPath":
     return polyline
 
 
-def dict_from_polyline(polyline: "itkt.PolylineParametricPath") -> dict:
+def dict_from_polyline(polyline: itkt.PolylineParametricPath) -> dict:
     """Serialize a Python itk.PolylineParametricPath object to a pickable Python dictionary."""
     import itk
 
@@ -1027,8 +1029,8 @@ def dict_from_polyline(polyline: "itkt.PolylineParametricPath") -> dict:
 
 
 def dict_from_transform(
-    transform: Union["itkt.TransformBase", list["itkt.TransformBase"]],
-) -> Union[list[dict], dict]:
+    transform: itkt.TransformBase | list[itkt.TransformBase],
+) -> list[dict] | dict:
     """Serialize a Python itk.Transform object to a pickable Python dictionary.
 
     If the transform is a list of transforms, then a list of dictionaries is returned.
@@ -1106,8 +1108,8 @@ def add_transform_dict(transform):
 
 
 def transform_from_dict(
-    transform_dict: Union[dict, list[dict]],
-) -> "itkt.TransformBase":
+    transform_dict: dict | list[dict],
+) -> itkt.TransformBase:
     """Deserialize a dictionary representing an itk.Transform object.
 
     If the dictionary represents a list of transforms, then a Composite Transform is returned.
@@ -1208,7 +1210,7 @@ def special_transform_check(transform_name):
     return transform
 
 
-def image_intensity_min_max(image_or_filter: "itkt.ImageOrImageSource"):
+def image_intensity_min_max(image_or_filter: itkt.ImageOrImageSource):
     """Return the minimum and maximum of values in a image of in the output image of a filter
 
     The minimum and maximum values are returned in a tuple: (min, max)
@@ -1236,10 +1238,10 @@ def range(image_or_filter):
 
 
 def imwrite(
-    image_or_filter: "itkt.ImageOrImageSource",
+    image_or_filter: itkt.ImageOrImageSource,
     filename: fileiotype,
     compression: bool = False,
-    imageio: Optional["itkt.ImageIOBase"] = None,
+    imageio: itkt.ImageIOBase | None = None,
 ) -> None:
     """Write a image or the output image of a filter to a file.
 
@@ -1278,12 +1280,12 @@ def imwrite(
 
 
 def imread(
-    filename: Union[fileiotype, Sequence[Union[str, os.PathLike]]],
-    pixel_type: Optional["itkt.PixelTypes"] = None,
+    filename: fileiotype | Sequence[str | os.PathLike],
+    pixel_type: itkt.PixelTypes | None = None,
     fallback_only: bool = False,
-    imageio: Optional["itkt.ImageIOBase"] = None,
-    series_uid: Optional[Union[int, str]] = None,
-) -> "itkt.ImageBase":
+    imageio: itkt.ImageIOBase | None = None,
+    series_uid: int | str | None = None,
+) -> itkt.ImageBase:
     """Read an image from a file or series of files and return an itk.Image.
 
     Parameters
@@ -1417,7 +1419,7 @@ def imread(
 
 
 def meshwrite(
-    mesh: "itkt.Mesh",
+    mesh: itkt.Mesh,
     filename: fileiotype,
     compression: bool = False,
     binary: bool = False,
@@ -1443,9 +1445,9 @@ def meshwrite(
 
 def meshread(
     filename: fileiotype,
-    pixel_type: Optional["itkt.PixelTypes"] = None,
+    pixel_type: itkt.PixelTypes | None = None,
     fallback_only: bool = False,
-) -> "itkt.Mesh":
+) -> itkt.Mesh:
     """Read a mesh from a file and return an itk.Mesh.
 
     The reader is instantiated with the mesh type of the mesh file if
@@ -1493,7 +1495,7 @@ def meshread(
     return reader.GetOutput()
 
 
-def transformread(filename: fileiotype) -> list["itkt.TransformBase"]:
+def transformread(filename: fileiotype) -> list[itkt.TransformBase]:
     """Read an itk Transform file.
 
     Parameters
@@ -1524,7 +1526,7 @@ def transformread(filename: fileiotype) -> list["itkt.TransformBase"]:
 
 
 def transformwrite(
-    transforms: Union["itkt.TransformBase", list["itkt.TransformBase"]],
+    transforms: itkt.TransformBase | list[itkt.TransformBase],
     filename: fileiotype,
     compression: bool = False,
 ) -> None:
@@ -1587,8 +1589,8 @@ def search(s: str, case_sensitive: bool = False) -> list[str]:  # , fuzzy=True):
 
 def set_inputs(
     new_itk_object,
-    inargs: Optional[Sequence[Any]] = None,
-    inkargs: Optional[dict[str, Any]] = None,
+    inargs: Sequence[Any] | None = None,
+    inkargs: dict[str, Any] | None = None,
 ):
     """Set the inputs of the given objects, according to the non named or the
     named parameters in args and kargs
@@ -1845,7 +1847,7 @@ def has_key(self, key: str):
     def __contains__(self, key: str):
         return key in self
 
-    def get(self, key: str, default: Optional[str] = None) -> Optional[str]:
+    def get(self, key: str, default: str | None = None) -> str | None:
         return self.get(key, default)
 
     def __len__(self):
@@ -1954,7 +1956,7 @@ def __call__(self, *args, **kargs):
         self.UpdateLargestPossibleRegion()
         return self
 
-    def expose(self, name: str, new_name: Optional[str] = None, position: int = -1):
+    def expose(self, name: str, new_name: str | None = None, position: int = -1):
         """Expose an attribute from a filter of the mini-pipeline.
 
         Once called, the pipeline instance has a new Set/Get set of methods to
@@ -2002,7 +2004,7 @@ def Stop() -> None:
         auto_pipeline.current = None
 
 
-def down_cast(obj: "itkt.LightObject"):
+def down_cast(obj: itkt.LightObject):
     """Down cast an itk.LightObject (or a object of a subclass) to its most
     specialized type.
     """
@@ -2232,7 +2234,7 @@ def template(cl):
     return itkTemplateBase.__template_instantiations_object_to_name__[class_(cl)]
 
 
-def ctype(s: str) -> "itkt.itkCType":
+def ctype(s: str) -> itkt.itkCType:
     """Return the c type corresponding to the string passed in parameter
 
     The string can contain some extra spaces.
diff --git a/Wrapping/Generators/Python/itk/support/init_helpers.py b/Wrapping/Generators/Python/itk/support/init_helpers.py
index 49c3f719562..4d8ddec97bf 100644
--- a/Wrapping/Generators/Python/itk/support/init_helpers.py
+++ b/Wrapping/Generators/Python/itk/support/init_helpers.py
@@ -1,6 +1,5 @@
 from sys import stderr as _system_error_stream
 from enum import IntEnum, unique
-from typing import Union
 
 __all__ = [
     "auto_not_in_place",
@@ -39,7 +38,7 @@ class AutoProgressTypes(IntEnum):
 
 
 def auto_progress(
-    progress_type: Union[bool, AutoProgressTypes] = AutoProgressTypes.TERMINAL,
+    progress_type: bool | AutoProgressTypes = AutoProgressTypes.TERMINAL,
 ) -> None:
     """Set up auto progress report
 
diff --git a/Wrapping/Generators/Python/itk/support/template_class.py b/Wrapping/Generators/Python/itk/support/template_class.py
index 96a765bf8b6..7698a85aa9f 100644
--- a/Wrapping/Generators/Python/itk/support/template_class.py
+++ b/Wrapping/Generators/Python/itk/support/template_class.py
@@ -23,7 +23,8 @@
 import types
 import collections
 import warnings
-from typing import Any, Callable, Union
+from typing import Any
+from collections.abc import Callable
 
 import itkConfig
 
@@ -299,7 +300,7 @@ def __local__init__(self, new_object_name: str) -> None:
         so that the singleton takes preference.
         Use this to define the class member elements
         """
-        self.__template__: dict[str, Union[str, Callable[..., Any]]] = (
+        self.__template__: dict[str, str | Callable[..., Any]] = (
             collections.OrderedDict()
         )
         self.__name__: str = new_object_name
diff --git a/Wrapping/Generators/Python/itk/support/types.py b/Wrapping/Generators/Python/itk/support/types.py
index cf5b9b307e1..f929d29361f 100644
--- a/Wrapping/Generators/Python/itk/support/types.py
+++ b/Wrapping/Generators/Python/itk/support/types.py
@@ -46,7 +46,6 @@
 class itkCType:
     # import locally to facilitate dynamic loading in itk/__init__.py
     import numpy as np
-    from typing import Optional
 
     __c_types__: dict[str, "itkCType"] = {}
     __c_types_for_dtype__: dict[str, np.dtype] = {}
@@ -71,7 +70,7 @@ def __repr__(self) -> str:
         return f"<itkCType {self.name}>"
 
     @staticmethod
-    def GetCType(name: str) -> Optional["itkCType"]:
+    def GetCType(name: str) -> "itkCType | None":
         # import locally to facilitate dynamic loading in itk/__init__.py
 
         """Get the type corresponding to the provided C primitive type name."""
@@ -90,7 +89,7 @@ def GetCType(name: str) -> Optional["itkCType"]:
             return None
 
     @staticmethod
-    def GetCTypeForDType(np_dtype: np.dtype) -> Optional["itkCType"]:
+    def GetCTypeForDType(np_dtype: np.dtype) -> "itkCType | None":
         """Get the type corresponding to the provided numpy.dtype."""
         try:
             return itkCType.__c_types_for_dtype__[np_dtype]
diff --git a/Wrapping/Generators/Python/itkConfig.py.in b/Wrapping/Generators/Python/itkConfig.template.in.py
similarity index 94%
rename from Wrapping/Generators/Python/itkConfig.py.in
rename to Wrapping/Generators/Python/itkConfig.template.in.py
index 4ed680c534f..1e68019fa54 100644
--- a/Wrapping/Generators/Python/itkConfig.py.in
+++ b/Wrapping/Generators/Python/itkConfig.template.in.py
@@ -34,7 +34,6 @@
   LazyLoading: Only load an itk library when needed. Before the library is
     loaded, the namespace will be inhabited with dummy objects."""
 
-from typing import Dict, List, Optional, Type, Union
 
 # User options
 SILENT: int = 0
@@ -51,6 +50,7 @@ def _get_environment_boolean(environment_var: str, default_string: str) -> bool:
     # False values are n, no, f, false, off and 0.
     # Raises ValueError if val is anything else.
     from os import environ as _environ
+
     def _strtobool(val: str) -> bool:
         val = val.lower()
         if val in ("y", "yes", "t", "true", "on", "1"):
@@ -60,7 +60,6 @@ def _strtobool(val: str) -> bool:
         else:
             raise ValueError(f"invalid truth value {val}")
 
-
     try:
         _StringDefault: str = _environ.get(environment_var, default_string)
         return bool(_strtobool(_StringDefault))
@@ -77,7 +76,9 @@ def _strtobool(val: str) -> bool:
     return bool(_strtobool(default_string))
 
 
-DefaultFactoryLoading: bool = _get_environment_boolean("ITK_PYTHON_DEFAULTFACTORYLOADING", "True")
+DefaultFactoryLoading: bool = _get_environment_boolean(
+    "ITK_PYTHON_DEFAULTFACTORYLOADING", "True"
+)
 LazyLoading: bool = _get_environment_boolean("ITK_PYTHON_LAZYLOADING", "True")
 NotInPlace: bool = _get_environment_boolean("ITK_PYTHON_NOTINPLACE", "False")
 del _get_environment_boolean
@@ -86,11 +87,11 @@ def _strtobool(val: str) -> bool:
 
 
 def _itk_format_warning(
-    message: Union[Warning, str],
-    category: Type[Warning],  # Ignore category
+    message: Warning | str,
+    category: type[Warning],  # Ignore category
     filename: str,  # Ignore filename
     lineno: int,  # Ignore lineno
-    line: Optional[str] = None,  # Ignore line
+    line: str | None = None,  # Ignore line
 ) -> str:
     """Format the warnings issued by itk to display only the message.
 
@@ -151,7 +152,7 @@ def _normalized_path(relative_posix_path: str, message) -> str:
 ITK_GLOBAL_VERSION_STRING: str = (
     "@ITK_VERSION_MAJOR@.@ITK_VERSION_MINOR@.@ITK_VERSION_PATCH@"
 )
-ITK_GLOBAL_WRAPPING_BUILD_OPTIONS: Dict[str, List[str]] = {
+ITK_GLOBAL_WRAPPING_BUILD_OPTIONS: dict[str, list[str]] = {
     "ITK_WRAP_IMAGE_DIMS": "@ITK_WRAP_IMAGE_DIMS@".split(";"),
     "WRAP_ITK_USIGN_INT": "@WRAP_ITK_USIGN_INT@".split(";"),
     "WRAP_ITK_SIGN_INT": "@WRAP_ITK_SIGN_INT@".split(";"),