CAR-NK cells show promise in cancer therapy, offering safer alternatives to CAR-T cells with fewer side effects. However, their poor homing and infiltration abilities in the tumor microenvironment limit effectiveness. Combining CAR-NK cells with therapies like anti-PD-1/PD-L1, radiotherapy, chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonists, oncolytic viruses, and photothermal therapy can enhance their proliferation, migration, and cytotoxicity. This review summarizes CAR-NK target selection, structure design, and combination strategies to overcome the inhibitory tumor microenvironment and improve therapeutic outcomes. CAR-NK cells target various antigens, including tumor-specific and associated antigens, and have shown efficacy in preclinical and clinical trials. They are safer than CAR-T cells, with fewer toxicities and better clinical applicability. However, challenges remain, such as tumor heterogeneity, immune suppression, and NK cell homing. Advances in CAR design, including fourth- and fifth-generation CARs, aim to improve NK cell function. Combination therapies with other treatments, such as radiotherapy and chemotherapy, enhance antitumor activity. Additionally, PD-1/PD-L1 inhibitors, proteasome inhibitors, and STING agonists improve NK cell function and tumor response. Oncolytic viruses and photothermal therapy also enhance immune responses. Despite these advancements, challenges like tumor microenvironment resistance and NK cell function remain. Future research aims to optimize CAR-NK therapy for solid tumors, improving safety and efficacy. This review highlights the potential of CAR-NK cells in cancer treatment and the need for further research to overcome current limitations.CAR-NK cells show promise in cancer therapy, offering safer alternatives to CAR-T cells with fewer side effects. However, their poor homing and infiltration abilities in the tumor microenvironment limit effectiveness. Combining CAR-NK cells with therapies like anti-PD-1/PD-L1, radiotherapy, chemotherapy, kinase inhibitors, proteasome inhibitors, STING agonists, oncolytic viruses, and photothermal therapy can enhance their proliferation, migration, and cytotoxicity. This review summarizes CAR-NK target selection, structure design, and combination strategies to overcome the inhibitory tumor microenvironment and improve therapeutic outcomes. CAR-NK cells target various antigens, including tumor-specific and associated antigens, and have shown efficacy in preclinical and clinical trials. They are safer than CAR-T cells, with fewer toxicities and better clinical applicability. However, challenges remain, such as tumor heterogeneity, immune suppression, and NK cell homing. Advances in CAR design, including fourth- and fifth-generation CARs, aim to improve NK cell function. Combination therapies with other treatments, such as radiotherapy and chemotherapy, enhance antitumor activity. Additionally, PD-1/PD-L1 inhibitors, proteasome inhibitors, and STING agonists improve NK cell function and tumor response. Oncolytic viruses and photothermal therapy also enhance immune responses. Despite these advancements, challenges like tumor microenvironment resistance and NK cell function remain. Future research aims to optimize CAR-NK therapy for solid tumors, improving safety and efficacy. This review highlights the potential of CAR-NK cells in cancer treatment and the need for further research to overcome current limitations.