Adoptive cell-based therapy offers a powerful approach for cancer treatment but remains limited by the complexity, cost, and safety concerns associated with genetic engineering of immune cells. Here, we present a biomaterial-based strategy to engineer natural killer (NK) cells without genetic modification. A series of DBCO-functionalized lipid biomaterials with distinct architectures were systematically evaluated for NK cell surface modification. A tadpole-shaped DSPE-PEG-Di-PEG-DBCO biomaterial demonstrated superior membrane anchoring, biocompatibility, and preservation of membrane integrity, enabling efficient conjugation of gemcitabine-loaded liposomes via bioorthogonal click chemistry. The resulting NK cell-drug conjugates retained high cell viability and exhibited enhanced cytotoxicity against pancreatic cancer cells through synergistic immune synapse formation and innate NK cell-mediated killing.