Over the past fifteen years, nanozymes—artificial nanomaterials with enzyme-like catalytic activity—have evolved from a laboratory phenomenon into one of the most rapidly advancing platforms in nanomedicine. The unique ability of nanozymes to selectively modulate the levels of reactive oxygen species within the tumor microenvironment opens fundamentally new avenues for highly selective therapy of malignant neoplasms. This review systematically presents current advances in the development of "smart" nanozymes for cancer treatment. Catalytic mechanisms are discussed in detail, including peroxidase-like, oxidase-like, catalase-like, superoxide dismutase-like, and hydrolase-like activities, as well as the factors influencing these processes. The main classes of nanozymes are analyzed: metals and metal oxides, carbon-based materials, metal-organic frameworks, single-atom catalysts, bimetallic and biomimetic systems. Strategies for enhancing catalytic efficiency are examined: heterometallic doping, defect engineering, surface modification, control of porosity and dimensionality, and the use of hybrid constructs with natural enzymes. Special attention is given to the integration of artificial intelligence and machine learning methods for predicting nanozyme structure and activity, thereby accelerating the search for optimal candidates. Therapeutic modalities are described—chemodynamic, photothermal, photodynamic, and sonodynamic therapy, depletion therapy, immunotherapy, as well as the induction of novel forms of cell death. It is shown that combined approaches, in which nanozymes perform multiple catalytic functions simultaneously, are the most effective. Finally, barriers to clinical translation are critically assessed: long-term biosafety, incomplete in vivo specificity, the challenge of scalable synthesis, and the lack of standardized evaluation protocols. Potential strategies to overcome these limitations are proposed.


