Abstract: Several metabolites associated with bioenergetics and biosynthesis, particularly intermediates from the mitochondrial tricarboxylic acid (TCA) cycle, such as succinate, fumarate, 2-hydroxyglutarate isomers (D-2-hydroxyglutarate and L-2-hydroxyglutarate), acetyl-CoA, and NADH/NADPH, may participate in cell malignant transformation. It has been proven that these metabolites exert “nonmetabolic” signaling functions during tumorigenesis. In this review, we will describe the advances in TCA cycle metabolites and tumor formation.