The chapter discusses the metabolic adaptations in cancer cells and their significance in tumor growth and potential for therapeutic intervention. It highlights the Warburg effect, where cancer cells exhibit increased aerobic glycolysis despite the presence of oxygen, generating energy and reducing ROS. The chapter also covers alternative glucose metabolism pathways, such as the pentose phosphate pathway, which produces NADPH and ribose sugars for nucleotide biosynthesis. The role of pyruvate kinase M2 (PKM2) in regulating glycolysis and promoting anabolic growth is emphasized. The PI3K pathway, which activates Akt1 and mTOR, is discussed as a key regulator of glucose uptake and anabolic processes. Hypoxia-induced transcription factors (HIFs) and the role of AMPK, p53, and FOXOs in counteracting the Warburg effect are also covered. The chapter further explores metabolic flexibility, such as the upregulation of carnitine palmitoyltransferase-1C (CPT1C) for fatty acid oxidation under stress conditions. Finally, it discusses the importance of NADPH in managing ROS and the role of isocitrate dehydrogenases in generating NADPH and producing 2-hydroxyglutarate, an oncometabolite. The chapter concludes by emphasizing the potential of these metabolic adaptations as therapeutic targets.The chapter discusses the metabolic adaptations in cancer cells and their significance in tumor growth and potential for therapeutic intervention. It highlights the Warburg effect, where cancer cells exhibit increased aerobic glycolysis despite the presence of oxygen, generating energy and reducing ROS. The chapter also covers alternative glucose metabolism pathways, such as the pentose phosphate pathway, which produces NADPH and ribose sugars for nucleotide biosynthesis. The role of pyruvate kinase M2 (PKM2) in regulating glycolysis and promoting anabolic growth is emphasized. The PI3K pathway, which activates Akt1 and mTOR, is discussed as a key regulator of glucose uptake and anabolic processes. Hypoxia-induced transcription factors (HIFs) and the role of AMPK, p53, and FOXOs in counteracting the Warburg effect are also covered. The chapter further explores metabolic flexibility, such as the upregulation of carnitine palmitoyltransferase-1C (CPT1C) for fatty acid oxidation under stress conditions. Finally, it discusses the importance of NADPH in managing ROS and the role of isocitrate dehydrogenases in generating NADPH and producing 2-hydroxyglutarate, an oncometabolite. The chapter concludes by emphasizing the potential of these metabolic adaptations as therapeutic targets.