Background <p>As an emerging type of immune cell therapy, chimeric antigen receptor natural killer (CAR-NK) cells have shown great potential in the treatment of both tumors and autoimmune diseases. Compared with CAR-T cells, CAR-NK cells have a lower risk of cytokine release syndrome and neurotoxicity and have the potential for “off-the-shelf” treatment from a wide range of sources including peripheral blood, umbilical cord blood, induction blood, and pluripotent stem cells (iPSCs).</p> Data sources <p>We systematically review the basic biological characteristics of CAR-NK cells, strategies for CAR construct design and optimization, cell sources and expansion techniques, gene transfer methods and the latest progress in preclinical and clinical research.</p> Results <p>CAR-NKs have shown good safety and preliminary efficacy in treating hematological malignancies, solid tumors, autoimmune diseases and infectious diseases. Challenges relating to persistence in the body and adaptability to the microenvironment of solid tumors remain, With continuous optimization of the genetic engineering, combination therapy and personalized strategies, CAR-NK therapy is expected to be an important pillar of the next generation of immunotherapies and promote the development of precision medicine.</p> Conclusions <p>CAR-NK cell therapy, with its superior safety profile and "off-the-shelf" potential, has emerged as a highly promising star in immunotherapy for tumors and autoimmune diseases. Although challenges remain in its in vivo persistence and efficacy against solid tumors, continuous engineering optimization and combination strategies are expected to advance the development of precision medicine.</p> Graphical abstract <p></p>