Natural Killer (NK) cells play a critical role in antitumor immunity through direct cytotoxic activity and secretion of immunoregulatory cytokines. They are particularly important in Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC), a key mechanism often leveraged by therapeutic antibodies. However, the conventional immunodeficient mouse models show limited capacity to support NK cell engraftment, restricting their translational relevance. To overcome this limitation, we developed two humanized cytokine-expressing immunodeficient NCG mouse models: NCG-hIL2 and NCG-hIL15, engineered to express human IL-2 and IL-15, respectively. NCG-hIL2 was well suited for evaluating ADCC antibodies like Trastuzumab, Margetuximab, Rituximab and Blinatumomab. Both NCG-hIL2 and NCG-hIL15 model offer powerful tools for investigating NK cell biology, cytokine-driven development, and immunotherapy evaluation.