Both cellular nutrient metabolism and chromatin organization are remodeled in cancer cells, and these alterations play key roles in tumor development and growth. Many chromatin modifying-enzymes utilize metabolic intermediates as cofactors or substrates, and recent studies have demonstrated that the epigenome is sensitive to cellular metabolism. The contribution of metabolic alterations to epigenetic deregulation in cancer cells is just beginning to emerge, as are the roles of the metabolism-epigenetics link in tumorigenesis. Here we review the roles of acetyl-CoA and S-adenosylmethionine (SAM), donor substrates for acetylation and methylation reactions, respectively, in regulating chromatin modifications in response to nutrient metabolism. We further discuss how oncogenic signaling, cell metabolism, and histone modifications are interconnected and how their relationship might impact tumor growth.