Previously, HO1 siRNA‐mediated chemo‐sensitization has been demonstrated in an AML xenograft model and AML patient bone marrow samples.[15] Here, we evaluated dual cell‐targeted HO1‐inhibition for a synergistic effect of chemo‐sensitization and immune reprogramming by using HO1 inhibitor‐loaded lipid‐polymer hNP. This evidence concerns the gene HMOX1 and acute myeloid leukemia.