Abstract. TP53 mutated myeloid neoplasms including acute myeloid leukemia (AML) and myelodysplastic neoplasms (MDS) are notoriously treatment resistant with uniformly poor outcomes. TP53 status is an important prognostic indicator and early knowledge of the of TP53 mutation/allelic state may assist in appropriate management including clinical trial enrollment for eligible patients. Thus far, no therapy has shown to demonstrate durable response or incremental survival benefit in TP53 mutated AML or MDS. Therefore, there is an urgent need for innovative therapies to improve the outcomes in this notoriously recalcitrant genomic subset. In this review, we dissect the biology, classification,prognosis, current treatment landscape, and the early phase evaluation of investigational agents in TP53 mutated AML and MDS.