Recent studies, including our own, have shown that targeting glycolysis can enhance antitumor immunity and improve immune checkpoint blockade (ICB) efficacy. We previously demonstrated that LDH inhibition with GNE-140 restores T cell cytotoxicity and infiltration while destabilizing Tregs, thereby enhancing ICB responses in glycolytic tumors such as melanoma and triple-negative breast cancer (TNBC). We therefore hypothesize that metabolic reprograming with LDH inhibition will potentiate adoptive cell transfer (ACT) therapy in melanoma and TNBC. Using both genetic (LDH-A knockdown) and pharmacological (GNE-140) approaches in TNBC 4T1 and melanoma B16 models, we are evaluating the impact of tumor glycolysis on ACT efficacy. We are assessing therapeutic effects and biodistribution of adoptively transferred tumor-specific T cells upon targeting LDH in vivo. Moreover, by ex vivo immune profiling we are investigating T-cell functional and metabolic phenotypes. Preliminary evidence in the B16 model suggests enhanced responsiveness of glycolysis‑low tumors to ACT with pre-activated CD8⁺ Pmel relative to glycolysis‑high tumors. Our findings aim to define how metabolic modulation via LDH inhibition can improve ACT outcomes in melanoma and TNBC, offering a novel combinatorial strategy for enhancing immunotherapy efficacy in solid tumors.