Patient-derived tumoroids, commonly referred to as cancer organoids, represent a promising avenue as cost-effective and biologically relevant cancer immunotherapy research models. In this study, we developed a proof-of-concept immunotherapy screening platform harnessing tumoroids to validate the cytotoxic activity of Natural Killer (NK) cells. Tumoroids were genetically engineered to create a GFP-expressing reporter pool that could be used to assess killing efficiency using live cell imaging platforms. We were able to demonstrate dose-dependent tumoroid killing with increasing effector-to-target ratios. This innovative approach holds the potential to streamline the engineering of patient-derived tumoroid models, facilitate the development of multiplex-killing assays, and provide an efficient tool for evaluating immunotherapies targeting solid tumors.