diff --git a/.github/workflows/unit-tests.yml b/.github/workflows/unit-tests.yml
index d2e2a170a1d04..842629ba331d6 100644
--- a/.github/workflows/unit-tests.yml
+++ b/.github/workflows/unit-tests.yml
@@ -430,20 +430,20 @@ jobs:
         with:
           fetch-depth: 0
 
-      - name: Set up Python for Pyodide
+      - name: Set up Python for pyodide-build
         id: setup-python
         uses: actions/setup-python@v5
         with:
-          python-version: '3.11.3'
+          python-version: '3.12'
 
       - name: Set up Emscripten toolchain
         uses: mymindstorm/setup-emsdk@v14
         with:
-          version: '3.1.46'
+          version: '3.1.58'
           actions-cache-folder: emsdk-cache
 
       - name: Install pyodide-build
-        run: pip install "pyodide-build==0.25.1"
+        run: pip install "pyodide-build>=0.29.2"
 
       - name: Build pandas for Pyodide
         run: |
@@ -452,10 +452,13 @@ jobs:
       - name: Set up Node.js
         uses: actions/setup-node@v4
         with:
-          node-version: '18'
+          node-version: '20'
 
       - name: Set up Pyodide virtual environment
+        env:
+          pyodide-version: '0.27.1'
         run: |
+          pyodide xbuildenv install ${{ env.pyodide-version }}
           pyodide venv .venv-pyodide
           source .venv-pyodide/bin/activate
           pip install dist/*.whl
diff --git a/.gitignore b/.gitignore
index a188e216d9f70..d951f3fb9cbad 100644
--- a/.gitignore
+++ b/.gitignore
@@ -137,3 +137,7 @@ doc/source/savefig/
 # Interactive terminal generated files #
 ########################################
 .jupyterlite.doit.db
+
+# Pyodide/WASM related files #
+##############################
+/.pyodide-xbuildenv-*
diff --git a/pandas/tests/series/indexing/test_setitem.py b/pandas/tests/series/indexing/test_setitem.py
index 158198239ba75..49c933c308235 100644
--- a/pandas/tests/series/indexing/test_setitem.py
+++ b/pandas/tests/series/indexing/test_setitem.py
@@ -9,7 +9,6 @@
 import numpy as np
 import pytest
 
-from pandas.compat import WASM
 from pandas.compat.numpy import np_version_gte1p24
 from pandas.errors import IndexingError
 
@@ -1449,7 +1448,6 @@ def obj(self):
                         np_version_gte1p24
                         and os.environ.get("NPY_PROMOTION_STATE", "weak") != "weak"
                     )
-                    or WASM
                 ),
                 reason="np.float32(1.1) ends up as 1.100000023841858, so "
                 "np_can_hold_element raises and we cast to float64",
diff --git a/web/pandas/pdeps/0010-required-pyarrow-dependency.md b/web/pandas/pdeps/0010-required-pyarrow-dependency.md
index d586c46e243f8..0c3bf3c776988 100644
--- a/web/pandas/pdeps/0010-required-pyarrow-dependency.md
+++ b/web/pandas/pdeps/0010-required-pyarrow-dependency.md
@@ -185,7 +185,6 @@ Additionally, if a user is installing pandas in an environment where wheels are
 the user will need to also build Arrow C++ and related dependencies when installing from source. These environments include
 
 - Alpine linux (commonly used as a base for Docker containers)
-- WASM (pyodide and pyscript)
 - Python development versions
 
 Lastly, pandas development and releases will need to be mindful of PyArrow's development and release cadance. For example when