Abstract: Metabolic remodeling, a well-recognized hallmark of cancer, provides biomass and energy to support the growing demand of unrestricted growth of cancer cells. In addition to metabolic supplies, the altered cell metabolism often results in the intracellular accumulation of particular metabolites. Recently, it is increasingly revealed these metabolites may exhibit metabolism-independent roles as signaling molecules, which triggers oncogenic signaling via various mechanisms including competitive inhibition, protein post-translational modifica-tions and direct protein binding. These insights provide a new perspective of metabolic remodeling in cancer progression. This review summarized the recent advancement in the understanding of metabolites as signaling molecules independent rewriting of metabolic pathways. By summarizing these progresses, this review hopes to provide a better understanding of tumor metabolic disturbance and to contribute to the discovery of novel potential therapeutic targets.