p53 plays a key role in tumor suppression. The tumor suppressive function of p53 has long been attributed to its ability to induce apoptosis, cell cycle arrest, and senescence in cells. However, recent studies suggest that other functions of p53 also contribute to its role as a tumor suppressor, such as its function in metabolic regulation. p53 regulates various metabolic pathways to maintain the metabolic homeostasis of cells and adapt cells to stress. In addition, recent studies have also shown that gain-of-function (GOF) mutant p53 proteins drive metabolic reprogramming in cancer cells, contributing to cancer progression. Further understanding of p53 and its GOF mutants in metabolism will provide new opportunities for cancer therapy.