NK-92 cell line is a promising alternative to primary NK cells for adoptive cell immunotherapy. NK-92 is approved by US-FDA for clinical trials, and offers a homogeneous, scalable source with unlimited proliferation, no donor variability, and no risk of donor-derived viral contamination. NK-92 cells also enable clonal selection after genome editing, ensuring safety, consistency, and enhanced functionality in therapeutic applications. However, their anti-cancer efficacy is limited by the absence of key activating receptors. To address this, we used CRISPR-mediated homology-directed repair to precisely integrate synthetic promoters and restore the expression of DNAM-1, CD16, and NKG2D, a critical receptor with broad specificity for stress-induced ligands. The engineered DNAM-1+, CD16+, and NKG2D-high NK-92 cells (termed NK-92 SPARK, short for Synthetic Promoters and Activating Receptor Knock-in) demonstrated markedly enhanced cytotoxicity against diverse cancer cell lines, including glioblastoma, pancreatic, ovarian, liver, and colon cancers. NK-92 SPARK can also perform antibody-dependent cellular cytotoxicity (ADCC) using therapeutic antibodies, broadening their specificity and anti-tumor efficacy.  Furthermore, we introduced membrane-bound IL-2 by fusing the IL-2 gene to the endogenous IL2RA locus, enabling autocrine signaling to support proliferation and survival without exogenous IL-2 supplementation. These modifications elevate the therapeutic potential of NK-92 SPARK to levels comparable to, or even exceeding, those of primary NK cells, providing a versatile and scalable platform for further genetic engineering, including the incorporation of chimeric antigen receptors (CAR). Our work demonstrates the transformative potential of CRISPR genome engineering in overcoming key limitations of NK-92 cells, enabling their use as a potent and adaptable tool for cancer immunotherapy.