Purine metabolism, a fundamental metabolic pathway governing nucleic acid synthesis, energy supply and cellular signaling, is aberrantly reprogrammed in tumor cells and acts as a critical driver of tumorigenesis and malignant progression. This review comprehensively summarizes the expression characteristics, regulatory mechanisms and specific roles of key enzymes involved in purine metabolism, such as phosphoribosyl pyrophosphate synthetase (PRPS), inosine monophosphate dehydrogenase (IMPDH), and adenosine deaminase (ADA), in the occurrence and development of various tumors, as well as recent advances in small-molecule inhibitors targeting these enzymes and evaluating their therapeutic potential and clinical application prospects in cancer treatment. Currently, a series of challenges remain, including diverse reactions, the interaction between tumor cells and the microenvironment, metabolic heterogeneity, and metabolic adaptability. Future research should focus on exploring precise regulatory networks of purine metabolism in tumors and developing novel highly selective inhibitors with low toxicity. This review aims to provide a comprehensive framework for understanding purine metabolic reprogramming and to support the development of novel metabolism-based anticancer strategies.