Background: Cancer cells can inhibit effector T cells through both immunomodulatory receptors and alteration of the tumor microenvironment. Rather than efficient use of aerobic glycolysis by activated effector T cells, Renal Cell Carcinoma (RCC) infiltrating T cells (TIL) fail to increase glucose metabolism, and instead display increased reactive oxygen species (ROS) and mitochondrial dysfunction. CD8 RCC TIL also have notable differences in mitochondrial morphology compared to healthy control CD8 T cells and were punctate and dispersed rather than fused in networks. Here we test if RCC TIL can be re-activated and identify metabolic requirements for inflammatory TIL function. Methods: De-identified samples from tumor or adjacent normal tissue donations from patients with RCC were collected under an approved IRB protocol and processed into single cell suspensions of tumor and associated cells by mechanical dissociation to test TIL activation and metabolic requirements upon in vitro re-stimulation. Results: RNA-seq data suggested that CD8 from TIL rely on distinct metabolic pathways compared to control. While control T cells increased effector cytokine production and glycolysis with antigen receptor alone and further augmented this pathway with co-stimulation, single cell RNAseq showed that CD8 RCC TIL required co-stimulation for this transition. Co-stimulation can promote T cell glycolysis and we found antigen receptor stimulation with CD28-mediated co-stimulation increased function of CD8 RCC TIL as indicated by increased surface markers of activation and IFNγproduction. This was accompanied by rescue of metabolic markers, including increased mitochondrial mass and markers of electron transport. Improved functional capacity was dependent upon glycolysis because inhibition with 2-deoxyglucose limited CD8 RCC TIL activation following CD28 co-stimulation. Conclusions: Bypassing metabolic defects restore markers of TIL activation and effector function.These datademonstrate that CD8 RCC TIL can be functionally restored but that this requires the ability to increase glucose metabolism. These findings may allow for combined therapies to improve response rates of checkpoint inhibition in this disease.