diff --git a/doc/source/whatsnew/v2.0.0.rst b/doc/source/whatsnew/v2.0.0.rst
index 3f1ac9bb18f75..f9561c9aa4325 100644
--- a/doc/source/whatsnew/v2.0.0.rst
+++ b/doc/source/whatsnew/v2.0.0.rst
@@ -719,6 +719,7 @@ Reshaping
 - Bug in :func:`join` when ``left_on`` or ``right_on`` is or includes a :class:`CategoricalIndex` incorrectly raising ``AttributeError`` (:issue:`48464`)
 - Bug in :meth:`DataFrame.pivot_table` raising ``ValueError`` with parameter ``margins=True`` when result is an empty :class:`DataFrame` (:issue:`49240`)
 - Clarified error message in :func:`merge` when passing invalid ``validate`` option (:issue:`49417`)
+- Bug in :meth:`DataFrame.explode` raising ``ValueError`` on multiple columns with ``NaN`` values or empty lists (:issue:`46084`)
 
 Sparse
 ^^^^^^
diff --git a/pandas/core/frame.py b/pandas/core/frame.py
index 5654ba469d05a..3b0beaa9d5373 100644
--- a/pandas/core/frame.py
+++ b/pandas/core/frame.py
@@ -8848,7 +8848,7 @@ def explode(
         if len(columns) == 1:
             result = df[columns[0]].explode()
         else:
-            mylen = lambda x: len(x) if is_list_like(x) else -1
+            mylen = lambda x: len(x) if (is_list_like(x) and len(x) > 0) else 1
             counts0 = self[columns[0]].apply(mylen)
             for c in columns[1:]:
                 if not all(counts0 == self[c].apply(mylen)):
diff --git a/pandas/tests/frame/methods/test_explode.py b/pandas/tests/frame/methods/test_explode.py
index 6d9874dc58c17..d1e4a603c5710 100644
--- a/pandas/tests/frame/methods/test_explode.py
+++ b/pandas/tests/frame/methods/test_explode.py
@@ -280,3 +280,24 @@ def test_multi_columns(input_subset, expected_dict, expected_index):
     result = df.explode(input_subset)
     expected = pd.DataFrame(expected_dict, expected_index)
     tm.assert_frame_equal(result, expected)
+
+
+def test_multi_columns_nan_empty():
+    # GH 46084
+    df = pd.DataFrame(
+        {
+            "A": [[0, 1], [5], [], [2, 3]],
+            "B": [9, 8, 7, 6],
+            "C": [[1, 2], np.nan, [], [3, 4]],
+        }
+    )
+    result = df.explode(["A", "C"])
+    expected = pd.DataFrame(
+        {
+            "A": np.array([0, 1, 5, np.nan, 2, 3], dtype=object),
+            "B": [9, 9, 8, 7, 6, 6],
+            "C": np.array([1, 2, np.nan, np.nan, 3, 4], dtype=object),
+        },
+        index=[0, 0, 1, 2, 3, 3],
+    )
+    tm.assert_frame_equal(result, expected)