This Special Issue aims to stimulate discussion and highlight the latest developments in understanding how and why metabolic reprogramming occurs in tumor cells and the molecular mechanisms linking altered metabolism to tumorigenesis and metastasis. Tumor cells undergo significant alterations in metabolic pathways, impacting growth, proliferation, invasion, treatment resistance, and metastasis. These changes arise from genetic mutations in cancer cells and the patient's metabolism, creating unique vulnerabilities that can be targeted for therapeutic strategies. In this Reprint, leading experts in this field share their cutting-edge research, key findings, and insight for the future to emphasize the centrality of metabolism in cancer biology and its potential as a target for personalized therapies, offering hope for improved patient outcomes through innovative treatment strategies that are able to enhance treatment efficacy and overcome resistance.