CAR-NK immunotherapy is a promising approach in tumor treatment, offering high efficiency and safety compared to CAR-T. This review discusses the application of CAR-NK in solid tumors, focusing on factors affecting its efficacy, such as hypoxia, metabolic factors, NK cell receptors, cytokines, and exosomes. It also explores the mechanisms and clinical potential of CAR-NK in treating various solid tumors. Challenges include the immunosuppressive tumor microenvironment (TME), which hinders CAR-NK function. Strategies to overcome these challenges include modifying CAR structures, enhancing NK cell activation, and improving TME conditions. CAR-NK therapy has shown potential in treating solid tumors like glioblastoma, lung cancer, breast cancer, gastric cancer, and colon cancer. Recent studies highlight the importance of targeting specific antigens and overcoming TME barriers. Clinical trials are ongoing, and further research is needed to optimize CAR-NK therapy for solid tumors. The review emphasizes the need for large-scale clinical trials to validate the efficacy and safety of CAR-NK in solid tumor treatment.CAR-NK immunotherapy is a promising approach in tumor treatment, offering high efficiency and safety compared to CAR-T. This review discusses the application of CAR-NK in solid tumors, focusing on factors affecting its efficacy, such as hypoxia, metabolic factors, NK cell receptors, cytokines, and exosomes. It also explores the mechanisms and clinical potential of CAR-NK in treating various solid tumors. Challenges include the immunosuppressive tumor microenvironment (TME), which hinders CAR-NK function. Strategies to overcome these challenges include modifying CAR structures, enhancing NK cell activation, and improving TME conditions. CAR-NK therapy has shown potential in treating solid tumors like glioblastoma, lung cancer, breast cancer, gastric cancer, and colon cancer. Recent studies highlight the importance of targeting specific antigens and overcoming TME barriers. Clinical trials are ongoing, and further research is needed to optimize CAR-NK therapy for solid tumors. The review emphasizes the need for large-scale clinical trials to validate the efficacy and safety of CAR-NK in solid tumor treatment.