Reframing Natural Killer Cell Biology for Cancer: From Cytotoxic Potential to Context‐Matched Immune States

Natural killer (NK) cells can eliminate malignant cells without prior sensitization, supporting their development as endogenous effectors and cellular therapies. Engineered and allogeneic platforms further extend this translational promise. Cytotoxic capacity alone, however, does not establish intratumoral competence, which also depends on access, localization, persistence, recognition, and resistance to local stress. This review reframes cancer NK biology around context‐matched immune states. It first defines circulating, tissue‐adapted, exposure‐conditioned, suppressed, and reprogrammed states and then explains how single‐cell, spatial, functional, and clinical evidence should be interpreted. It next examines how tumor‐intrinsic recognition, stromal architecture, suppressive cellular circuits, and metabolic adversity shape NK‐cell behavior. Hematologic and solid malignancies are compared as distinct but overlapping design contexts. Engineering strategies are evaluated by the barriers they address, followed by a preservation, restoration, and replacement or bypass framework for state switching. Finally, candidate biomarkers, representative clinical studies, and multi‐level endpoints connect delivery, state, local biological effect, and clinical outcome. This evidence‐calibrated framework does not define a clinical standard; it provides a testable basis for aligning NK‐cell products, tumor ecology, and translational evaluation and for designing interpretable clinical studies across disease settings.