Abstract: Although immunotherapy has made a breakthrough in the treatment of cancer, the emergence of drug resistance has limited benefits in most patients, and reversing immunotherapy resistance remains a hotly debated and unresolved issue. The tumor microenvironment (TME) comprises a large number of T lymphocytes. During the biological processes of proliferation, activation, and the effect of tumor-infiltrating lymphocytes (TILs), TILs face severe local metabolic stress, resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements. This process of adaptive changes in the metabolic pattern is closely related to the phenotype and function of TILs, affecting immunotherapy efficacy and mediating immunotherapy resistance. In recent years, with the study of TIL metabolism and the search for specific metabolic regulatory points, targeting the TIL metabolic pathway could restore the tumor-killing function and reverse immunotherapy resistance. This review explores the relationship between the metabolic reprogramming of TILs and immune resistance, and provides a new strategy for reversing immune resistance.