Allogeneic cellular immunotherapies have the potential to revolutionize cancer treatment due to their cost-effectiveness, scalability, and on-demand availability. However, the immunogenicity and limited persistence of allogeneic cells remain significant obstacles to achieving sustained, robust antitumor responses with these therapies. A common strategy to address immunogenicity has been genetic knockout of HLA molecules, which efficiently abrogates T cell-mediated rejection in the recipient, but triggers rejection by natural killer (NK) cells via missing-self recognition. Our lab has previously demonstrated that knocking out key adhesion ligands within the immune synapse, specifically ICAM-1 and CD58, broadly protects allogeneic iPSC-derived NK cells from host NK cell-mediated rejection and increases persistence in vivo. Here, we developed a one-shot approach for adhesion ligand knockdown combined with CD19-targeted chimeric antigen receptor (CAR19) expression by incorporating microRNA-based shRNAs targeting ICAM-1 and CD58 into a CAR plasmid. The shRNA sequences and construct design were optimized for simultaneous knockdown and CAR19 expression as assessed by flow cytometry-based screens. Functional experiments showed that engineering NK cells with these one-shot constructs mitigated their rejection by host NK cells and T cells as shown by flow cytometry-based killing assays. Additionally, NK cell killing of CD19⁺ tumors was enhanced by the expression of CAR19, together demonstrating the ability to multiplex shRNA-based protein knockdown and drive functional CAR expression, all off a single promoter. This approach was evaluated in our primary adaptive NK cell therapy platform (ADAPT-NK), which is poised to enter clinical trials, thereby making significant progress towards the development of highly potent, immune-evasive ADAPT-NK cells for use as an off-the-shelf cancer immunotherapy.