Despite synthetic lethality targeting the mediators of MTp53-associated cancer metabolism portends a bright future for innumerable cancer patients with TP53 mutation, the diverse nature of MTp53, the intracellular intricate regulatory networks accounting for the modulation of metabolism, and the extrinsic environmental factors determine together with the specific synthetic lethal partners to a specific type of MTp53, making identifying the synthetic lethal partners a quite challenging work. This evidence concerns the gene TP53 and cancer.