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By leveraging large\u2010scale multi\u2010omics and single\u2010cell RNA sequencing (scRNA\u2010seq), we characterize the tumor microenvironment of HR\n                    <jats:sup>+<\/jats:sup>\n                    \/HER2\n                    <jats:sup>\u2212<\/jats:sup>\n                    breast cancer, revealing that an abundance of activated natural killer (NK) cells correlates with favorable anti\u2010PD\u2010(L)1 responses. Our preclinical models demonstrate that immunotherapy enhances NK cell cytotoxicity and immunomodulatory functions, thereby impeding tumor growth. Furthermore, drug screening of cell lines and patient\u2010derived tumors reveals that platinum enhances NK cell cytotoxicity, potentially via the NF\u2010\u03baB pathway, creating synergy with immunotherapy. Consistent with these findings, a clinical cohort analysis shows an increased proportion of activated NK cells in tumors following platinum\u2010based chemotherapy. 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