Abstract: Tumor cells with altered energy metabolism phenotypes compared with normally differentiated adult cells were found. These tumor cells consume more glucose via the glycolytic pathway and produce more secreted lactate, and rarely use oxidative phosphorylation (OXPHOS) to generate more adenosine triphosphate (P^lrP). Nevertheless, the definitive molecular mechanism of the increased glycolysis by this energy metabolism phenotype in the tumor cells remains unclear. The high glycolytic activity of the tumor cells might be involved in the overexpression of glycolytic enzymes and glucose transporters, low OXPHOS expression and transport proteins, as well as the reduced number of mitoehondria per cell and increased mitoehondrial DNA sensitivity to oxidative stress. However, heterogeneity was observed in the genes, the biochemistry, and the morphology of the tumor cells. The elevated glycolytic activity has its own comprehensive mechanism. In this review, we analyzed various genetic and biochemical mechanisms by which tumor cells achieve enhanced glycolytic activity. Furthermore, the proposed mechanisms that lead to decreased mitochondrial metabolism and OXPHOS in tumor cells are also discussed. The energy metabolism system is could be used as an alternative therapeutic target for treating glycolytic tumors.