diff --git a/homeassistant/util/package.py b/homeassistant/util/package.py
index 4d87e51badc..3796bf35cd7 100644
--- a/homeassistant/util/package.py
+++ b/homeassistant/util/package.py
@@ -8,6 +8,7 @@ from importlib.metadata import PackageNotFoundError, version
 import logging
 import os
 from pathlib import Path
+import site
 from subprocess import PIPE, Popen
 import sys
 from urllib.parse import urlparse
@@ -83,6 +84,12 @@ def is_installed(requirement_str: str) -> bool:
         return False
 
 
+_UV_ENV_PYTHON_VARS = (
+    "UV_SYSTEM_PYTHON",
+    "UV_PYTHON",
+)
+
+
 def install_package(
     package: str,
     upgrade: bool = True,
@@ -96,7 +103,18 @@ def install_package(
     """
     _LOGGER.info("Attempting install of %s", package)
     env = os.environ.copy()
-    args = ["uv", "pip", "install", "--quiet", package]
+    args = [
+        "uv",
+        "pip",
+        "install",
+        "--quiet",
+        package,
+        # We need to use unsafe-first-match for custom components
+        # which can use a different version of a package than the one
+        # we have built the wheel for.
+        "--index-strategy",
+        "unsafe-first-match",
+    ]
     if timeout:
         env["HTTP_TIMEOUT"] = str(timeout)
     if upgrade:
@@ -104,10 +122,20 @@ def install_package(
     if constraints is not None:
         args += ["--constraint", constraints]
     if target:
-        assert not is_virtual_env()
-        # This only works if not running in venv
-        args += ["--user"]
-        env["PYTHONUSERBASE"] = os.path.abspath(target)
+        abs_target = os.path.abspath(target)
+        args += ["--target", abs_target]
+    elif (
+        not is_virtual_env()
+        and not (any(var in env for var in _UV_ENV_PYTHON_VARS))
+        and (abs_target := site.getusersitepackages())
+    ):
+        # Pip compatibility
+        # Uv has currently no support for --user
+        # See https://github.com/astral-sh/uv/issues/2077
+        # Using workaround to install to site-packages
+        # https://github.com/astral-sh/uv/issues/2077#issuecomment-2150406001
+        args += ["--python", sys.executable, "--target", abs_target]
+
     _LOGGER.debug("Running uv pip command: args=%s", args)
     with Popen(
         args,
diff --git a/tests/util/test_package.py b/tests/util/test_package.py
index 72600f94890..59a02bff838 100644
--- a/tests/util/test_package.py
+++ b/tests/util/test_package.py
@@ -93,7 +93,15 @@ def test_install(mock_popen: MagicMock, mock_env_copy: MagicMock) -> None:
     assert package.install_package(TEST_NEW_REQ, False)
     assert mock_popen.call_count == 2
     assert mock_popen.mock_calls[0] == call(
-        ["uv", "pip", "install", "--quiet", TEST_NEW_REQ],
+        [
+            "uv",
+            "pip",
+            "install",
+            "--quiet",
+            TEST_NEW_REQ,
+            "--index-strategy",
+            "unsafe-first-match",
+        ],
         stdin=PIPE,
         stdout=PIPE,
         stderr=PIPE,
@@ -111,7 +119,15 @@ def test_install_with_timeout(mock_popen: MagicMock, mock_env_copy: MagicMock) -
     assert mock_popen.call_count == 2
     env["HTTP_TIMEOUT"] = "10"
     assert mock_popen.mock_calls[0] == call(
-        ["uv", "pip", "install", "--quiet", TEST_NEW_REQ],
+        [
+            "uv",
+            "pip",
+            "install",
+            "--quiet",
+            TEST_NEW_REQ,
+            "--index-strategy",
+            "unsafe-first-match",
+        ],
         stdin=PIPE,
         stdout=PIPE,
         stderr=PIPE,
@@ -134,6 +150,8 @@ def test_install_upgrade(mock_popen, mock_env_copy) -> None:
             "install",
             "--quiet",
             TEST_NEW_REQ,
+            "--index-strategy",
+            "unsafe-first-match",
             "--upgrade",
         ],
         stdin=PIPE,
@@ -145,12 +163,26 @@ def test_install_upgrade(mock_popen, mock_env_copy) -> None:
     assert mock_popen.return_value.communicate.call_count == 1
 
 
-def test_install_target(mock_sys, mock_popen, mock_env_copy, mock_venv) -> None:
+@pytest.mark.parametrize(
+    "is_venv",
+    [
+        True,
+        False,
+    ],
+)
+def test_install_target(
+    mock_sys: MagicMock,
+    mock_popen: MagicMock,
+    mock_env_copy: MagicMock,
+    mock_venv: MagicMock,
+    is_venv: bool,
+) -> None:
     """Test an install with a target."""
     target = "target_folder"
     env = mock_env_copy()
-    env["PYTHONUSERBASE"] = os.path.abspath(target)
-    mock_venv.return_value = False
+    abs_target = os.path.abspath(target)
+    env["PYTHONUSERBASE"] = abs_target
+    mock_venv.return_value = is_venv
     mock_sys.platform = "linux"
     args = [
         "uv",
@@ -158,7 +190,10 @@ def test_install_target(mock_sys, mock_popen, mock_env_copy, mock_venv) -> None:
         "install",
         "--quiet",
         TEST_NEW_REQ,
-        "--user",
+        "--index-strategy",
+        "unsafe-first-match",
+        "--target",
+        abs_target,
     ]
 
     assert package.install_package(TEST_NEW_REQ, False, target=target)
@@ -169,12 +204,83 @@ def test_install_target(mock_sys, mock_popen, mock_env_copy, mock_venv) -> None:
     assert mock_popen.return_value.communicate.call_count == 1
 
 
-@pytest.mark.usefixtures("mock_sys", "mock_popen", "mock_env_copy", "mock_venv")
-def test_install_target_venv() -> None:
-    """Test an install with a target in a virtual environment."""
-    target = "target_folder"
-    with pytest.raises(AssertionError):
-        package.install_package(TEST_NEW_REQ, False, target=target)
+@pytest.mark.parametrize(
+    ("in_venv", "additional_env_vars"),
+    [
+        (True, {}),
+        (False, {"UV_SYSTEM_PYTHON": "true"}),
+        (False, {"UV_PYTHON": "python3"}),
+        (False, {"UV_SYSTEM_PYTHON": "true", "UV_PYTHON": "python3"}),
+    ],
+    ids=["in_venv", "UV_SYSTEM_PYTHON", "UV_PYTHON", "UV_SYSTEM_PYTHON and UV_PYTHON"],
+)
+def test_install_pip_compatibility_no_workaround(
+    mock_sys: MagicMock,
+    mock_popen: MagicMock,
+    mock_env_copy: MagicMock,
+    mock_venv: MagicMock,
+    in_venv: bool,
+    additional_env_vars: dict[str, str],
+) -> None:
+    """Test install will not use pip fallback."""
+    env = mock_env_copy()
+    env.update(additional_env_vars)
+    mock_venv.return_value = in_venv
+    mock_sys.platform = "linux"
+    args = [
+        "uv",
+        "pip",
+        "install",
+        "--quiet",
+        TEST_NEW_REQ,
+        "--index-strategy",
+        "unsafe-first-match",
+    ]
+
+    assert package.install_package(TEST_NEW_REQ, False)
+    assert mock_popen.call_count == 2
+    assert mock_popen.mock_calls[0] == call(
+        args, stdin=PIPE, stdout=PIPE, stderr=PIPE, env=env, close_fds=False
+    )
+    assert mock_popen.return_value.communicate.call_count == 1
+
+
+def test_install_pip_compatibility_use_workaround(
+    mock_sys: MagicMock,
+    mock_popen: MagicMock,
+    mock_env_copy: MagicMock,
+    mock_venv: MagicMock,
+) -> None:
+    """Test install will use pip compatibility fallback."""
+    env = mock_env_copy()
+    mock_venv.return_value = False
+    mock_sys.platform = "linux"
+    python = "python3"
+    mock_sys.executable = python
+    site_dir = "/site_dir"
+    args = [
+        "uv",
+        "pip",
+        "install",
+        "--quiet",
+        TEST_NEW_REQ,
+        "--index-strategy",
+        "unsafe-first-match",
+        "--python",
+        python,
+        "--target",
+        site_dir,
+    ]
+
+    with patch("homeassistant.util.package.site", autospec=True) as site_mock:
+        site_mock.getusersitepackages.return_value = site_dir
+        assert package.install_package(TEST_NEW_REQ, False)
+
+    assert mock_popen.call_count == 2
+    assert mock_popen.mock_calls[0] == call(
+        args, stdin=PIPE, stdout=PIPE, stderr=PIPE, env=env, close_fds=False
+    )
+    assert mock_popen.return_value.communicate.call_count == 1
 
 
 @pytest.mark.usefixtures("mock_sys", "mock_venv")
@@ -202,6 +308,8 @@ def test_install_constraint(mock_popen, mock_env_copy) -> None:
             "install",
             "--quiet",
             TEST_NEW_REQ,
+            "--index-strategy",
+            "unsafe-first-match",
             "--constraint",
             constraints,
         ],