The article reviews the advancements and challenges in CAR-NK (Chimeric Antigen Receptor Natural Killer) therapy for solid tumors. CAR-NK therapy, a promising method in tumor immunotherapy, has shown high safety and efficiency compared to CAR-T therapy. The review focuses on the construction of CAR-NK, the impact of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on CAR-NK efficacy, and its application in various solid tumors. Key mechanisms such as the role of NKG2D, KIR, DNAM-1, and NCR receptors are discussed, along with the effects of TGF-β, IL-2, IL-15, and IL-12 cytokines. The article also highlights the potential of exosomes in enhancing CAR-NK activity. Clinical trials and experimental studies are reviewed, demonstrating the therapeutic potential of CAR-NK in treating solid tumors like glioblastoma, lung cancer, breast cancer, gastric cancer, colon cancer, liver cancer, and pancreatic cancer. Despite the progress, challenges remain, including optimizing transduction efficiency, overcoming the immunosuppressive microenvironment, and improving cell persistence. The article concludes by outlining future directions and the need for further research to enhance the effectiveness of CAR-NK therapy in solid tumor treatment.The article reviews the advancements and challenges in CAR-NK (Chimeric Antigen Receptor Natural Killer) therapy for solid tumors. CAR-NK therapy, a promising method in tumor immunotherapy, has shown high safety and efficiency compared to CAR-T therapy. The review focuses on the construction of CAR-NK, the impact of hypoxia and metabolic factors, NK cell surface receptors, cytokines, and exosomes on CAR-NK efficacy, and its application in various solid tumors. Key mechanisms such as the role of NKG2D, KIR, DNAM-1, and NCR receptors are discussed, along with the effects of TGF-β, IL-2, IL-15, and IL-12 cytokines. The article also highlights the potential of exosomes in enhancing CAR-NK activity. Clinical trials and experimental studies are reviewed, demonstrating the therapeutic potential of CAR-NK in treating solid tumors like glioblastoma, lung cancer, breast cancer, gastric cancer, colon cancer, liver cancer, and pancreatic cancer. Despite the progress, challenges remain, including optimizing transduction efficiency, overcoming the immunosuppressive microenvironment, and improving cell persistence. The article concludes by outlining future directions and the need for further research to enhance the effectiveness of CAR-NK therapy in solid tumor treatment.