CD8⁺ T cells are central players in controlling infections and cancer. Longevity, functionality, and metabolic fitness are critical determinants of T cell efficacy in cancer immunotherapy. Tumor-infiltrating CD8⁺ T cells undergo metabolic ‘exhaustion' in the nutrient- and oxygen-deprived tumor microenvironment (TME). Thus, reprograming CD8⁺ T cell metabolism may provide important therapeutic strategies for cancer treatment. Indeed, the adoptive transfer of memory CD8⁺ T cells with sustained metabolic fitness may yield better antitumor protection in both mouse models and the clinic. Here, we discuss recent progress on how cellular metabolism is linked to CD8⁺ T cell fate decisions and on how metabolic intermediates can impact gene expression via modulation of the epigenome. We examine the feasibility of developing potential strategies to improve antitumor immunity through the modulation of T cell metabolic activity.