Mutations in the KRAS oncogene are present in >90% of pancreatic ductal adenocarcinomas (PDAC), a highly aggressive cancer which has a 5-year survival of 13%, that remains refractory to immunotherapy. Recent development of mutant-selective inhibitors targeting the KRAS oncoprotein have provided a new therapeutic avenue. In this study, we investigate inhibiting mutant KRAS to enhance response to Natural Killer (NK) cell therapy in PDAC. By surveying 178 PDAC patients in The Cancer Genome Atlas, we found that higher expression of the NK cell marker, NCAM1 (CD56), is associated with improved patient survival (44mo vs. 16mo, P<0.0001), suggesting that greater NK cell infiltration may be beneficial. Peripheral blood NK cells demonstrated natural cytotoxic activity against PDAC cells in Incucyte in vitro tumor killing assays, which was enhanced by up to 2-fold in combination with KRASi. Furthermore, KRASi enhanced NK cell motility against tumor cells in an engineered 3D collagen matrix, suggesting a chemoattractant/chemotaxis effect. Mechanistically, through a combination of qRT-PCR, cytokine array and RNA-sequencing, we found that KRASi upregulates expression of ULBP1-6 NK cell activating ligands on tumor cells, and increases production of pro-inflammatory cytokines/chemokines such as CXCL10, CXCL11, CCL2, CXCL5, CCL20, and IL15 PDAC cells. In line with these findings and our 3D motility results, Transwell assays demonstrated increased NK cell migration towards tumor cells treated with KRASi. Lastly, to further enhance NK cell homing and tumor killing, we employed a Tri-specific killer engager (TriKE) which targets B7-H3, a molecule selectively expressed on tumor cells. NK cells with TriKE treatment delivered superior tumor killing and enhanced motility in 3D matrices. TriKE treatment synergized with KRASi, achieving 90-98% tumor cell killing. Overall, our study provides rationale and mechanistic insights for subsequent ongoing pre-clinical in vivo studies to evaluate KRASi and NK cell therapy for PDAC.