Ferroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation, distinct from other forms of cell death. It plays a critical role in cancer progression and therapy. Cancer metabolism, including carbohydrate, amino acid, and lipid metabolism, interacts with ferroptosis. Carbohydrate metabolism influences ferroptosis through glycolysis, the TCA cycle, and the pentose phosphate pathway. For instance, glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) regulate ferroptosis by modulating glutathione peroxidase 4 (GPX4) activity and SLC7A11 expression. The TCA cycle enzymes, such as alpha-ketoglutarate dehydrogenase complex (KGDH) and succinate dehydrogenase (SDH), also influence ferroptosis by affecting lipid peroxidation and ROS levels. The pentose phosphate pathway produces NADPH, which is essential for maintaining glutathione (GSH) levels and suppressing ferroptosis. Amino acid metabolism also plays a key role in ferroptosis. Glutathione, synthesized from glutamate, cysteine, and glycine, is a major antioxidant that protects against ferroptosis. Cysteine deprivation reduces GSH synthesis and increases lipid peroxidation, promoting ferroptosis. Methionine metabolism supports GPX4 activity, while enzymes like cystathionine beta-synthase (CBS) and glutamic pyruvic transaminase 2 (GPT2) regulate cysteine and GSH levels, influencing ferroptosis. The amino acid metabolism also affects the expression of SLC7A11, a key transporter for cystine, which is essential for maintaining GSH levels. Lipid metabolism is central to ferroptosis. Phospholipids, particularly those containing polyunsaturated fatty acids (PUFAs), are susceptible to lipid peroxidation, which triggers ferroptosis. Enzymes like acyl-CoA synthetases (ACSLs) and lipoxygenases (LOXs) contribute to lipid peroxidation, while antioxidants such as reduced glutathione (GSH), ubiquinol (CoQH2), and tetrahydrobiopterin (BH4) suppress ferroptosis. The metabolism of fatty acids, including their synthesis, elongation, and desaturation, influences ferroptosis by affecting lipid peroxidation and ROS levels. Cholesterol metabolism also plays a role in ferroptosis, as cholesterol can modulate lipid rafts and influence the availability of iron and fatty acids. The interplay between cancer metabolism and ferroptosis presents opportunities for therapeutic intervention. Targeting ferroptosis through metabolic pathways, such as enhancing GSH production orFerroptosis is a regulated form of cell death driven by iron-dependent lipid peroxidation, distinct from other forms of cell death. It plays a critical role in cancer progression and therapy. Cancer metabolism, including carbohydrate, amino acid, and lipid metabolism, interacts with ferroptosis. Carbohydrate metabolism influences ferroptosis through glycolysis, the TCA cycle, and the pentose phosphate pathway. For instance, glycolytic enzymes like hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) regulate ferroptosis by modulating glutathione peroxidase 4 (GPX4) activity and SLC7A11 expression. The TCA cycle enzymes, such as alpha-ketoglutarate dehydrogenase complex (KGDH) and succinate dehydrogenase (SDH), also influence ferroptosis by affecting lipid peroxidation and ROS levels. The pentose phosphate pathway produces NADPH, which is essential for maintaining glutathione (GSH) levels and suppressing ferroptosis. Amino acid metabolism also plays a key role in ferroptosis. Glutathione, synthesized from glutamate, cysteine, and glycine, is a major antioxidant that protects against ferroptosis. Cysteine deprivation reduces GSH synthesis and increases lipid peroxidation, promoting ferroptosis. Methionine metabolism supports GPX4 activity, while enzymes like cystathionine beta-synthase (CBS) and glutamic pyruvic transaminase 2 (GPT2) regulate cysteine and GSH levels, influencing ferroptosis. The amino acid metabolism also affects the expression of SLC7A11, a key transporter for cystine, which is essential for maintaining GSH levels. Lipid metabolism is central to ferroptosis. Phospholipids, particularly those containing polyunsaturated fatty acids (PUFAs), are susceptible to lipid peroxidation, which triggers ferroptosis. Enzymes like acyl-CoA synthetases (ACSLs) and lipoxygenases (LOXs) contribute to lipid peroxidation, while antioxidants such as reduced glutathione (GSH), ubiquinol (CoQH2), and tetrahydrobiopterin (BH4) suppress ferroptosis. The metabolism of fatty acids, including their synthesis, elongation, and desaturation, influences ferroptosis by affecting lipid peroxidation and ROS levels. Cholesterol metabolism also plays a role in ferroptosis, as cholesterol can modulate lipid rafts and influence the availability of iron and fatty acids. The interplay between cancer metabolism and ferroptosis presents opportunities for therapeutic intervention. Targeting ferroptosis through metabolic pathways, such as enhancing GSH production or