This study establishes the PROTAC cocktail of CRBN‐based dAurA383 and cIAP‐based dAurA450 as a promising spatial‐temporal drug administration strategy to sequentially eliminate the multifaceted functions of mitotic AURKA and interphase AURKA, relieve the hook effect, and prevent cancer stem cell‐mediated drug resistance in acute myeloid leukemia. This evidence concerns the gene AURKA and acute myeloid leukemia.