Natural killer (NK) cells are characterized by their ability to recognize and eliminate tumor cells and virus-infected cells. In addition, they produce cytokines such as interferon (IFN)-gamma and skew the adaptive immune response towards a Th1/proinflammatory and cytotoxic profile due to the establishment of a reciprocal crosstalk with dendritic cells and macrophages. The understanding of the factors that affect the activation and development of effector functions of NK cells has led to their positioning as forefront runners for the development of immunotherapy strategies in the field of immuno-oncology. In this context, our laboratory investigates the cellular and molecular mechanisms that affect the ability of NK cells to recognize and eliminate tumor cells, develops activities aimed at the identification and validation of new molecular targets in immuno-oncology and how to capitalize on the acquired knowledge to exploit, by using monoclonal antibodies, the therapeutic potential of NK cells for the treatment of cancer patients.