P53 is a key factor encoded by the TP53, and it prevents cells from becoming cancerous and has a wide range of powerful functions. p53 is found to play an important role in inducing DNA repair, apoptosis, cell cycle arrest and senescence, and the loss of these functions does not abrogate P53’s tumor suppressive activity. Metabolism is the basis of life, and metabolic abnormalities can lead to a variety of diseases, including tumors, and is one of the main drivers of cancer progression. It has recently been discovered that P53 plays a key role in regulating metabolism. P53-mediated regulation of cell metabolism is a fundamental mechanism controlling cancer occurrence and development and contributes to its tumor suppressive activity. Here, this article reviewed the relationship between P53 and glucose, fatty acid, amino acid and nucleotide metabolism, and discussed the complex mechanism and the latest research progress of P53 in the metabolic regulation in tumor development.