Immune checkpoint blockade inhibition is a therapy which interferes with inhibitory signals placed upon immune cells, thereby eliciting anti-tumor responses. Although programmed death-1(PD-1)blockade therapy has been shown to be highly effective in clinical use, certain population of patients still fail to respond. Therefore, it is critical to determine how therapeutic efficacy of checkpoint inhibition can be enhanced. Recently, it has been shown that intracellular metabolism plays an important role in T cell differentiation and function. Because an effective tumor response relies on the differentiation of tumor-responsive effector cytotoxic T lymphocytes(CTLs), understanding such mechanisms will be essential for developing an improved therapeutic approach. Experiments on tumor-bearing mice have displayed strong anti-tumor responses upon combination therapy ofPD -1 blockade and enhanced mitochondrial metabolism, through increased production ofreactive oxygen species(ROS); upregulation ofmechanistic target ofrapamycin(mTOR)and AMP-activated protein kinase(AMPK); and upregulation ofperoxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1a). In addition, the use of bezafibrate, a peroxisome proliferator-activated receptor(PPAR)agonist, in combination with PD-1 blockade resulted in improved effector function in CTLs. In this review, we will explore the mechanism behind T cell metabolism under the context ofcheckpoint blockade therapy, as well as how modulating T cell metabolism yields synergistic anti-tumor effects in combination with PD-1 blockade therapy.