Abstract: The sequential launch of chimeric antigen receptor T-cell (CAR-T cell) therapy products caused a breakthrough in the treatment of hematological tumors. However, owing to the differences in properties between solid tumors and hematological tumors, CAR-T cell shave not been used much in the treatment of solid tumors. Solid tumor cells themselves and their distinctive tumor microenvironment (TME) are two crucial factors limiting the efficacy of CAR-T cells by impairing their function in multiple processes, including their infiltration into the tumor site, maintenance of their anti-antitumor activity in the TME, and targeted recognition killing of tumor cells. To address these problems, an increasing number of preclinical studies have proposed potential effective solutions, and corresponding clinical studies also have been carried out. This manuscript focuses on reviewing the existing challenges and corresponding optimization strategies for CAR-T cells in solid tumor treatment, aiming to provide a reference for future exploration of its applications.