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Relapse of AML after allogeneic HSCT poses significant challenges with poor outcomes, requiring an individualized approach that considers disease biology, patient fitness, and relapse timing. This review aims to guide treatment by exploring strategies like immunosuppression tapering, advanced chemotherapies, targeted genomic therapies, and cellular interventions such as donor lymphocyte infusions or second transplants. Emerging tools like MRD monitoring and innovative therapies, including checkpoint inhibitors and engineered T-cells, are transforming care, with a focus on improving survival while aligning with patient goals and quality of life.