Cytokines are critical mediators of immune communication and valuable therapeutic targets. This study reveals that natural killer (NK) cells primed with 25 kDa branched polyethylenimine (Chem_NK) enhance the tumor-homing capabilities of control NK cells (C_NK) through cytokine-driven interactions. Adoptive transfer of Chem_NK into nude mice significantly increased endogenous NK cell infiltration into xenografted tumors. Chem_NK-conditioned media (CM) educated C_NK by upregulating chemokine receptor expression via an ERK1/2 signaling-dependent mechanism, improving their migration toward cancer cells. Moreover, direct injection of Chem_NK CM into a lung metastasis syngeneic mouse model enhanced chemokine receptor expression in endogenous NK cells, resulting in increased tumor infiltration and suppression of lung metastases. Depletion of endogenous NK cells completely abolished the therapeutic effect of Chem_NK CM, demonstrating that the therapeutic efficacy primarily stems from the Chem_NK CM-mediated activation of endotenous NK cells. These findings underscore the potential of Chem_NK secretomes to amplify the tumor-homing activity of other NK cells and exert robust anti-tumor effects. Additionally, Chem_NK provide a promising model system for studying immune communication between activated NK cells and their neighboring NK cells, paving the way for novel cancer immunotherapies.