CRISPR/Cas9 has recently emerged as a powerful technique for genetic modification. This technology relies on the introduction of Cas9 protein in conjunction with guide RNA into the NK cells. More recently, CRISPR/Cas9 has also been applied to introduce new genes. In parallel to CRISPR/Cas9, a homologous donor DNA template is introduced in the same cell via transfection.This DNA template replaces the targeted gene, thus allowing for the introduction of genes that promote the anti-tumor effects.  When the CAR gene is delivered via viral vectors or using transposon-based random insertion, expression levels are variable. CAR expression driven by an endogenous promotor following CRISPR/Cas9-specific locus knock-in strategies could result in long CAR-T persistence in vivo, with a memory-like phenotype and less expression of exhaustion markers.Thus, the CRISPR/Cas9 strategy is a versatile technique that should be further explored for the generation of CAR-NK cells. It can be used to precisely delete, repair or introduce genes in a specific locus, hence holding promise to generate powerful anti-tumor NK cells.