Tumor immunotherapy has achieved impressive therapeutic effects in clinical practice and has attracted increasing attention. Among them, chimeric antigen receptor T (CAR-T) cell therapy has made breakthrough progress in the treatment of hematological malignancies. However, with prolonged exposure to tumor antigens, CAR-T cells may become exhausted in vivo. The exhaustion of CAR-T cells can lead to poor treatment efficacy or tumor recurrence. The mechanism of CAR-T cell exhaustion involves a series of processes, such as the expression of exhaustion-associated transcription factors, the role of the immunosuppressive tumor microenvironment, and the influence of CAR structure itself. Here, we summarize the process and underlying mechanisms of CAR-T cell exhaustion, as well as potential solutions to improve T cell exhaustion and enhance the efficacy of CAR-T cell therapy, with the aim of expanding the application of CAR-T cell therapy in tumor treatment.