Long‐term survival of adult patients with acute myeloid leukemia (AML) remains unsatisfactory.We describe the results of a mechanistic and efficacy study combining venetoclax (ABT‐199), a recently approved BCL2 inhibitor, and the clinical stage CD33‐targeting antibody radiolabeled with 225Actinium (225Ac‐lintuzumab) in two venetoclax‐resistant AML models in vitro and in vivo. The gene discussed is BCL2; the disease is acute myeloid leukemia.