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However, its clinical efficacy remains limited by the immunosuppressive tumor microenvironment (TME), which restricts immune cells infiltration, suppresses effector cells activity, and promotes immune escape. Recent advances in catalytic nanomedicine have highlighted single\u2010atom nanozymes (SAzymes) as a promising platform for overcoming these barriers. Owing to their atomic precision and tunable electronic structure, SAzymes exhibit highly efficient enzyme\u2010like catalytic activities and enable precise regulation of the TME. Through catalytic therapy, SAzymes can alleviate hypoxia, regulate lactate accumulation, disrupt redox homeostasis, and reprogram immunosuppressive immune cells populations. Importantly, SAzyme\u2010mediated catalytic therapy can induce immunogenic cell death (ICD), thereby enhancing antitumor immune responses. In addition, the well\u2010defined atomic architecture of SAzymes provides a unique opportunity to establish quantitative structure\u2013activity relationships (QSAR), enabling rational optimization of catalytic performance through modulation of their composition and coordination environment. This review systematically summarizes the mechanisms by which SAzymes remodel the TME and enhance cancer immunotherapy, discussing recent advances in atomic level design principles and multimodal synergistic therapy. 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