Metabolic reprogramming is a hallmark of malignancy, with cancer cells reprogramming their metabolism to support growth and proliferation. This reprogramming involves aerobic glycolysis, glutamine catabolism, macromolecular synthesis, and redox homeostasis, which are under cell-autonomous control by oncogenic signaling and transcriptional networks. While many metabolic inhibitors have advanced into clinical trials, recent research suggests that cancer metabolism is flexible and context-specific, with few fixed, broadly applicable liabilities. Metabolic heterogeneity among human tumors and within distinct regions of the same tumor is increasingly recognized, challenging the classical paradigm of convergent, oncogene-driven liabilities. As tumors progress from premalignant lesions to metastatic cancer, their metabolic phenotypes and vulnerabilities evolve, influenced by microenvironmental and genetic factors. Metabolic reprogramming during cancer progression is complex, with pathways that support localized tumor growth distinct from those that drive metastasis and therapy resistance. Understanding how metabolic phenotypes evolve as cancer progresses is crucial for developing effective therapeutic strategies. Recent advances in metabolic analysis and in vivo studies have revealed that cancer cells require many of the same pathways as nonmalignant tissues, indicating that few metabolic activities are truly confined to tumors. Metabolic heterogeneity among tumors and within the same tumor is a challenge for developing therapies that exploit metabolic vulnerabilities. The emerging view is that cancer metabolism is flexible and context-specific, with some of the most promising therapeutic targets distinct from pathways that support cell growth in culture or locally aggressive tumors. Metabolic reprogramming in cancer is influenced by both cell-intrinsic and cell-extrinsic factors, and understanding these factors is essential for developing effective therapies. Metabolic reprogramming in cancer is a dynamic process that evolves as tumors progress, with different metabolic dependencies emerging at different stages of cancer progression. The metabolic needs and vulnerabilities of cancer cells change as they progress from premalignant lesions to metastatic cancer, with distinct metabolic liabilities in primary tumors and metastatic cancer. Metabolic reprogramming in cancer is a complex process that involves multiple pathways and is influenced by both cell-intrinsic and cell-extrinsic factors. Understanding the metabolic changes that occur during cancer progression is essential for developing effective therapeutic strategies. Metabolic reprogramming in cancer is a dynamic process that evolves as tumors progress, with different metabolic dependencies emerging at different stages of cancer progression. The metabolic needs and vulnerabilities of cancer cells change as they progress from premalignant lesions to metastatic cancer, with distinct metabolic liabilities in primary tumors and metastatic cancer. Metabolic reprogramming in cancer is a complex process that involves multiple pathways and is influenced by both cell-intrinsic and cell-extrinsic factors. Understanding the metabolic changes that occur during cancer progression is essential for developing effective therapeutic strategies.Metabolic reprogramming is a hallmark of malignancy, with cancer cells reprogramming their metabolism to support growth and proliferation. This reprogramming involves aerobic glycolysis, glutamine catabolism, macromolecular synthesis, and redox homeostasis, which are under cell-autonomous control by oncogenic signaling and transcriptional networks. While many metabolic inhibitors have advanced into clinical trials, recent research suggests that cancer metabolism is flexible and context-specific, with few fixed, broadly applicable liabilities. Metabolic heterogeneity among human tumors and within distinct regions of the same tumor is increasingly recognized, challenging the classical paradigm of convergent, oncogene-driven liabilities. As tumors progress from premalignant lesions to metastatic cancer, their metabolic phenotypes and vulnerabilities evolve, influenced by microenvironmental and genetic factors. Metabolic reprogramming during cancer progression is complex, with pathways that support localized tumor growth distinct from those that drive metastasis and therapy resistance. Understanding how metabolic phenotypes evolve as cancer progresses is crucial for developing effective therapeutic strategies. Recent advances in metabolic analysis and in vivo studies have revealed that cancer cells require many of the same pathways as nonmalignant tissues, indicating that few metabolic activities are truly confined to tumors. Metabolic heterogeneity among tumors and within the same tumor is a challenge for developing therapies that exploit metabolic vulnerabilities. The emerging view is that cancer metabolism is flexible and context-specific, with some of the most promising therapeutic targets distinct from pathways that support cell growth in culture or locally aggressive tumors. Metabolic reprogramming in cancer is influenced by both cell-intrinsic and cell-extrinsic factors, and understanding these factors is essential for developing effective therapies. Metabolic reprogramming in cancer is a dynamic process that evolves as tumors progress, with different metabolic dependencies emerging at different stages of cancer progression. The metabolic needs and vulnerabilities of cancer cells change as they progress from premalignant lesions to metastatic cancer, with distinct metabolic liabilities in primary tumors and metastatic cancer. Metabolic reprogramming in cancer is a complex process that involves multiple pathways and is influenced by both cell-intrinsic and cell-extrinsic factors. Understanding the metabolic changes that occur during cancer progression is essential for developing effective therapeutic strategies. Metabolic reprogramming in cancer is a dynamic process that evolves as tumors progress, with different metabolic dependencies emerging at different stages of cancer progression. The metabolic needs and vulnerabilities of cancer cells change as they progress from premalignant lesions to metastatic cancer, with distinct metabolic liabilities in primary tumors and metastatic cancer. Metabolic reprogramming in cancer is a complex process that involves multiple pathways and is influenced by both cell-intrinsic and cell-extrinsic factors. Understanding the metabolic changes that occur during cancer progression is essential for developing effective therapeutic strategies.