Fueling the fatal voyage: How metabolic plasticity empowers every step of cancer metastasis

Metastasis is the primary cause of cancer mortality, a complex cascade driven by intertwined cellular adaptability and microenvironmental reprogramming. Although its mechanistic origins are multifactorial and context-dependent, metabolic plasticity, manifested by dynamic shifts in glycolysis, lipid oxidation, amino acid utilization, and mitochondrial bioenergetics, is increasingly recognized as a central orchestrator of metastatic progression. Emerging therapeutic strategies that target these metabolic adaptations, such as diet-exercise modulation, nanotechnology-enabled pathway inhibition, and metabolite neutralization, show promise for disrupting metastatic niches and enhancing immune surveillance. This review synthesizes the systemic and spatial roles of metabolism across the metastatic cascade to advocate a fundamental reconceptualization of metastasis as a metabolically programmable process. Future efforts should focus on mapping the dynamic heterogeneity of tumor metabolism to develop stage-specific, ecologically informed interventions against disseminated disease.