Natural killer cells are a promising cell source for developing chimeric antigen receptor (CAR) based therapies since they exhibit antitumor responses in the absence of the side effects associated with CAR-T cells. Besides, the lack of T-cell receptors in NK cells allows the generation of allogeneic cell products without inducing graft-versus-host disease in infused patients. Despite the success of the first clinical trial with antiCD19-CAR-NK cells against CD19+ malignancies, the search for improvements in these CAR-NK products is one of the main goals. The discovery of memory-like responses in NK cells that resemble the trained immunity of the myeloid compartment have redefined their functional complexity and heterogeneity. However, this phenomenon in the context of CAR-NK products as well as its impact in the clinical outcome in infused patients remains unexplored. We aim to characterize this memory phenotype including the regulatory network that governs this process. Indeed, we have already assessed the functionality of memory responses in human primary NK cells repeatedly exposed to tumor cells, including non-transduced and CAR19-NK cells.  We identified the modulation of several activation/inhibitory receptors along with a significant impact in the inflammatory output. Moreover, the same modulation was observed in human NK cell that were frozen after the first exposure to a tumor cell line, suggesting that these long-lasting secondary responses rely on epigenetic marks preserved during freezing/thawing. Thus, the characterization of memory-like responses in CAR-NK products may open a new avenue to find molecular traits to improve the efficacy and safety of these cell products.