Although natural killer (NK) cells exhibit antigen-independent cytotoxicity, their efficacy in non-small cell lung cancer is limited by poor tumor targeting and weak immune synapse formation. Here, we developed a lipid biomaterial platform for rapid, non-genetic surface engineering of both cancer and NK cells to enhance their physical interactions. The lipid biomaterials incorporate lipid anchor and complementary dibenzocyclooctyne (DBCO) or azide (N₃) groups to enable bioorthogonal click reactions at cell-cell interfaces. DBCO-N₃-mediated interaction reinforced immune synapse formation, enhanced NK cell activation, and increased cytotoxicity against lung cancer cells. Furthermore, Lipid-N₃ successfully labeled 3D lung tumoroids within collagen hydrogels, enabling enhanced antitumor activity of engineered NK cells in a biomimetic TME. This lipid-mediated engineering strategy provides a versatile and translational approach to improve NK cell-based immunotherapy for solid tumors.