Macrophages are a heterogeneous population of immune cells that play diverse roles in homeostasis and immune responses. They can be categorized into two main phenotypes: pro-inflammatory (M1) and anti-inflammatory/pro-resolving (M2). M1 macrophages are involved in initiating and sustaining inflammation, while M2 macrophages promote tissue repair and resolution of inflammation. These phenotypes are associated with distinct metabolic profiles. M1 macrophages primarily use glycolysis and have a disrupted TCA cycle, leading to the accumulation of itaconate and succinate, which stabilize HIF1α and support glycolytic metabolism. In contrast, M2 macrophages rely on oxidative phosphorylation (OXPHOS) and have an intact TCA cycle, supporting fatty acid oxidation and OXPHOS. Metabolic adaptations are crucial for macrophage function and polarization. The review discusses recent findings linking macrophage functions and metabolism, highlighting the importance of metabolic reprogramming in macrophage responses. Key metabolic pathways include glycolysis, the pentose phosphate pathway (PPP), and the Krebs cycle. These pathways are regulated by various transcription factors and signaling pathways, such as NF-κB, STAT, and HIF1α. The review also explores the roles of amino acid and lipid metabolism in macrophage function, emphasizing their importance in immune responses and tissue homeostasis. Overall, the metabolic signature of macrophage responses is essential for their functional diversity and adaptation to different microenvironments.Macrophages are a heterogeneous population of immune cells that play diverse roles in homeostasis and immune responses. They can be categorized into two main phenotypes: pro-inflammatory (M1) and anti-inflammatory/pro-resolving (M2). M1 macrophages are involved in initiating and sustaining inflammation, while M2 macrophages promote tissue repair and resolution of inflammation. These phenotypes are associated with distinct metabolic profiles. M1 macrophages primarily use glycolysis and have a disrupted TCA cycle, leading to the accumulation of itaconate and succinate, which stabilize HIF1α and support glycolytic metabolism. In contrast, M2 macrophages rely on oxidative phosphorylation (OXPHOS) and have an intact TCA cycle, supporting fatty acid oxidation and OXPHOS. Metabolic adaptations are crucial for macrophage function and polarization. The review discusses recent findings linking macrophage functions and metabolism, highlighting the importance of metabolic reprogramming in macrophage responses. Key metabolic pathways include glycolysis, the pentose phosphate pathway (PPP), and the Krebs cycle. These pathways are regulated by various transcription factors and signaling pathways, such as NF-κB, STAT, and HIF1α. The review also explores the roles of amino acid and lipid metabolism in macrophage function, emphasizing their importance in immune responses and tissue homeostasis. Overall, the metabolic signature of macrophage responses is essential for their functional diversity and adaptation to different microenvironments.