Metabolic reprogramming is a hallmark of cancer that promotes elevated glycolysis, depleting nutrients in the tumor microenvironment (TME) and impairing T cell metabolism and function. Although T cell–based therapies, including chimeric antigen receptor (CAR) T cells and tumor-infiltrating lymphocytes (TILs), have shown clinical promise, their efficacy in solid tumors remains limited by the hostile TME. Here, we investigated how glucose availability shapes T cell–based therapy responses in melanoma. Using a CD19⁺ melanoma model, we found that both CD19‑28ζ and CD19‑BBζ CAR T cells exhibited reduced cytotoxicity under glucose restriction or following lactate dehydrogenase (LDH) inhibition, despite distinct intrinsic metabolic programs. To restore T cell function under glucose restriction, we screened a Sulfur-Triazole Exchange (SuTEx) covalent probe library in antigen-specific OT-I T cells, identifying probe G6 as a lead compound that increased glucose dependence and enhanced cytotoxicity. In CAR T cells, G6 selectively improved cytotoxicity within the CD8⁺ population, indicating a CD8-specific advantage. Proteomic profiling identified carnitine palmitoyltransferase 1A (CPT1A) as a putative G6 target, implicating fatty acid oxidation in this metabolic adaptation. Consistent with this mechanism, pharmacologic inhibition of CPT1A with etomoxir phenocopied the effects of G6 and markedly improved CD8⁺ CAR T cell cytotoxicity under glucose restriction. These findings identify targetable metabolic pathways to enhance T cell fitness in nutrient-poor environments, providing rationale for metabolic rewiring strategies to improve T cell–based immunotherapy efficacy in solid tumors.