Natural killer (NK) cells are innate lymphoid cells that display potent anti-cancer activity against leukaemia. Clinical trials have demonstrated the power and safety of allogeneic NK cell transfer in the context of cancer immunotherapy, with the absence of several potentially fatal toxicities. However, generating sufficient cells from healthy donors for adoptive cell therapy is challenging. The NK cell line, NK-92, displays robust and reproducible potent anti-cancer cytotoxicity and has emerged as a promising alternative for the development of an NK cell based “off-the-shelf” immunotherapy. However, the therapeutic efficacy of these cells is limited by several barriers. These include i) the upregulation of inhibitory pathways, ii) inadequate target recognition, and iii) reduced antibody-dependent responses. To augment this, we have established a powerful and robust Cas9 ribonucleoprotein (RNP)-based homology directed repair (HDR) CRISPR protocol for the development of genetically modified NK-92 cells. We first utilised this platform to knock-out NKG2A, encoding the critical NKG2A inhibitory receptor, in both wildtype NK-92 cells and NK-92 cells engineered to express a CD19 chimeric antigen receptor. These armoured NK-92 cells are now equipped with enhanced capacity to eliminate leukaemia. To further boost NK-92 anti-cancer function, we optimised our engineering platform to knock-in a green fluorescent protein to the NKG2A locus. Currently, we are applying this protocol to knock-in a non-cleavable CD16 variant to enhance antibody-dependent responses. This work is among the first to utilise cutting-edge HDR CRISPR technology to produce next generation armoured NK cells for cancer immunotherapy and provides a promising foundation for future research.