Objective To systematically summarize the role of immune cells in the progression of anastomotic leak (AL) following colorectal cancer (CRC) surgery, with an emphasis on the molecular mechanisms of metabolic reprogramming in relevant immune cells, aiming to provide new insights for the diagnosis and treatment of AL. MethodWe reviewed recent literature on the metabolic reprogramming of immune cells in AL following CRC surgery. ResultsIn the postoperative CRC AL microenvironment, homeostasis imbalance drives metabolic reprogramming of immune cells (macrophages, neutrophils), manifested as enhanced glycolysis, impaired fatty acid oxidation, and tricarboxylic acid cycle disruption. Accumulated metabolites (lactate, succinate), along with acidic pH, hypoxia, and immune factors, collectively shape an intertwined immunosuppressive and pro-inflammatory microenvironment that impedes anastomotic healing. Targeting key nodes in this metabolic reprogramming offers potential therapeutic strategies and a theoretical framework for clinical translation in AL. ConclusionsImmune cells, as key components of the AL microenvironment, play an important role in the initiation and progression of AL. In-depth exploration of the molecular mechanisms underlying metabolic reprogramming of relevant immune cells may provide directions for the diagnosis and treatment of AL, with the aim of improving patients’ outcomes.