Aerobic glycolysis, one of the most important metabolic features of tumor cells, can not only provide energy immediately, but also generate a number of glycolytic intermediates which are diverse biosynthetic precursors. More importantly, high flux of glycolysis causes the high⁃lactate, low⁃glucose metabolic environment which is conducive to maintain the immunosuppressive tumor microenvironment. Aerobic glycolysis accompanied with the upregulated key enzymes and transporters which result in increased glucose consumption and lactic acid secretion. Targeting glycolysis⁃related gene can inhibit tumor progression and improve the sensitivity of other therapeutic medicine. The combination of targeted glycolysis therapy and other therapies such as immunotherapy and chemotherapy will be promising in tumor therapy. However, targeted glycolysis therapy has two main challenges: ① metabolic heterogeneity of tumor cells; ② the damage to the immune system. This article reviews the research progress of various targets and their targeted medicine of aerobic glycolysis as well as the difficulties of targeted glycolysis therapy.