Myeloid malignancies include various types of cancers that arise from abnormal development or proliferation of myeloid cells within the bone marrow. Chimeric antigen receptor (CAR) T cell treatments, which show great potential for B cell and plasma cell cancers, face major challenges when used for myeloid malignancies. CAR natural killer (NK) cell-based immunotherapy encounters several challenges in treating myeloid cancers, including: (1) poor gene transfer efficiency and expansion platforms in vitro, (2) limited proliferation and persistence in vivo, (3) antigenic heterogeneity, and (4) an immunosuppressive tumor microenvironment. Despite these hurdles, "off-the-shelf" CAR-NK treatments showed encouraging results, marked by enhanced proliferation, prolonged persistence, enhanced tumor infiltration, and improved adaptability. This review offers a summary of the biological traits and cellular sources of NK cells along with a discussion of contemporary CAR designs. Furthermore, it addresses the challenges observed in preclinical research and clinical trials of CAR-NK cell therapy for myeloid cancers, suggesting enhancement strategies.