This review article explores the role of 3-phosphoglycerate dehydrogenase (PHGDH) in cancer metabolism and its potential as a therapeutic target. PHGDH is a key enzyme in the serine biosynthesis pathway, which is crucial for DNA synthesis and antioxidant production in cancer cells. Elevated PHGDH activity is observed in various cancers and is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. This elevated activity contributes to cancer growth, progression, metastasis, and drug resistance. The review highlights the structural aspects of PHGDH, its involvement in one-carbon metabolism, and its potential as a therapeutic target. It also discusses the effects of PHGDH inhibitors on cancer cell growth and the development of innovative treatment strategies. The article emphasizes the importance of understanding PHGDH's role in cancer to improve therapeutic approaches and overcome resistance mechanisms.This review article explores the role of 3-phosphoglycerate dehydrogenase (PHGDH) in cancer metabolism and its potential as a therapeutic target. PHGDH is a key enzyme in the serine biosynthesis pathway, which is crucial for DNA synthesis and antioxidant production in cancer cells. Elevated PHGDH activity is observed in various cancers and is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. This elevated activity contributes to cancer growth, progression, metastasis, and drug resistance. The review highlights the structural aspects of PHGDH, its involvement in one-carbon metabolism, and its potential as a therapeutic target. It also discusses the effects of PHGDH inhibitors on cancer cell growth and the development of innovative treatment strategies. The article emphasizes the importance of understanding PHGDH's role in cancer to improve therapeutic approaches and overcome resistance mechanisms.