The review discusses the significance of tumor glycolysis as a therapeutic target in cancer. It highlights the altered energy metabolism in cancer cells, characterized by their preference for glycolysis over oxidative phosphorylation, despite being less efficient. This metabolic phenotype is crucial for cancer cell growth and survival, as it provides energy and supports macromolecular biosynthesis. The review also emphasizes the role of glycolytic enzymes and their non-glycolytic functions in cancer, such as transcriptional regulation and redox balance. Recent studies have shown that targeting glycolysis can disrupt cancer cell growth and enhance chemosensitivity. The review discusses various molecular targets and inhibitors of glycolysis, including hexokinase II (HKII), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase M2 (PK-M2), and lactate dehydrogenase (LDH). Preclinical investigations have demonstrated the effectiveness of these targets in cancer therapy, with some showing promising clinical potential. The review concludes by discussing the challenges and future directions in targeting tumor glycolysis, including the development of selective inhibitors and the potential for combination therapies.The review discusses the significance of tumor glycolysis as a therapeutic target in cancer. It highlights the altered energy metabolism in cancer cells, characterized by their preference for glycolysis over oxidative phosphorylation, despite being less efficient. This metabolic phenotype is crucial for cancer cell growth and survival, as it provides energy and supports macromolecular biosynthesis. The review also emphasizes the role of glycolytic enzymes and their non-glycolytic functions in cancer, such as transcriptional regulation and redox balance. Recent studies have shown that targeting glycolysis can disrupt cancer cell growth and enhance chemosensitivity. The review discusses various molecular targets and inhibitors of glycolysis, including hexokinase II (HKII), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase M2 (PK-M2), and lactate dehydrogenase (LDH). Preclinical investigations have demonstrated the effectiveness of these targets in cancer therapy, with some showing promising clinical potential. The review concludes by discussing the challenges and future directions in targeting tumor glycolysis, including the development of selective inhibitors and the potential for combination therapies.