Managing acute myeloid leukemia (AML) and its critical complications requires understanding the complex interplay between disease biology, treatment strategies, and patient characteristics. Complications like sepsis, acute respiratory failure (ARF), hyperleukocytosis, coagulopathy, tumor lysis syndrome (TLS) and central nervous system (CNS) involvement present unique challenges needing precise evaluation and tailored interventions. Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches. As the microbiological landscape evolves and new therapeutic agents emerge, adapting strategies to mitigate harmful pharmacological interactions is crucial. Advances in understanding the genetic profiles of patients with hyperleukocytosis contribute to better-targeted therapeutic strategies. Effective AML management relies on collaborative efforts from hematologists, specialized services, and intensive care units (ICUs). This review analyzes recent data on critical AML complications, identifies areas for further investigation, and proposes ways to advance clinical research and enhance patient care strategies.