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As a class of artificial enzyme mimics, nanozymes combine the unique properties of nanomaterials with the catalytic functions of natural enzymes. In recent years, with the rapid development of nanomedicine and nanocatalytic technology, metal-hybridized nanoenzymes (MHNs) have shown great potential with excellent catalytic properties and good biocompatibility, providing new ideas and reference solutions for cancer diagnosis and treatment. This review introduces the latest progress of MHNs, focuses on their specific applications in cancer diagnosis and treatment, explores their potential in cancer marker detection, bioimaging, tumor microenvironment (TME) response, cellular level detection, and provides an in-depth analysis of how MHNs can regulate the TME with their catalytic activity and synergistically enhance the anticancer effect in combination with various means, such as immunotherapy and photothermal therapy (PTT). In addition, we will discuss the key issues and future development directions of current research and breakthroughs in the clinical translation of key bottlenecks, in order to lay the foundation for the promotion of the practical application of MHNs in cancer therapy. MHNs serve as multifunctional platforms for early cancer detection, encompassing biomarker detection, bioimaging, TME response, and cellular level detection. Simultaneously, their catalytic activity modulates the TME and synergizes with immunotherapy, PTT, and gene therapy to enhance cancer treatment efficacy. This article details the design, mechanisms of action, and efficacy of MHNs in cancer diagnosis and treatment. These strategies significantly enhance the performance of MHNs, thereby advancing their development toward integrated diagnosis and therapy. • Development, properties, and advantages of MHNs. • Comparative analysis of different MHNs in cancer diagnosis and therapy. • Current clinical translation prospects and challenges of MHNs.