A hallmark of the cancer cells is the reprogramming energy metabolism, a process crucial to carcinogenesis and tumor development. Emerging evidence consistently demonstrates the antitumoral effects of physical exercise observed in both experimental animal models and humans. One plausible explanation for the antitumor benefits of exercise is related to energy metabolism. In this view, physical exercise can cause global metabolic changes in the body, as well as modulate tumor metabolism. However, the pathway by which exercise modulates tumor development is still poorly understood. Here, we discuss the metabolic alterations occurring in both the body and cancer cells, examining how physical exercise contributes to antitumoral effects by modulating the tissues, metabolic hormones, and metabolites, including the impact of exercise on mitochondrial function in cancer cells. The influence of physical exercise on both body metabolism and tumor energy metabolism presents an opportunity for a deeper understanding of cancer biology. It also opens avenues for the development of targeted investigations focused on unraveling the intricacies of tumor energy metabolism.