Recent studies underscore the role of transcription factor Nrf2 and the emerging class of BH3 mimetics in overcoming chemoresistance in acute myeloid leukemia (AML). Nrf2 modulates cellular defense mechanisms that impede chemotherapy efficacy, while BH3 mimetics target apoptotic pathways to induce leukemia cell death. These advances offer a promising horizon for improving AML treatment outcomes amid persistent resistance challenges.