Nanozymes, engineered nanomaterials that mimic natural enzyme activity, have emerged as powerful tools in precision cancer therapy due to their ability to generate reactive oxygen species (ROS), modulate the tumor microenvironment (TME), and facilitate cascade catalytic reactions. This review presents a comprehensive evaluation of recent innovations in nanozyme structural engineering aimed at improving catalytic performance, substrate specificity, and biocompatibility. Key design strategies, including dimensional tailoring, valence state tuning, and surface functionalisation, are discussed in the context of tumor-targeted therapies. Special focus is given to multifunctional and stimuli-responsive nanozymes that adapt to TME conditions or external triggers like light and pH. Despite significant progress, barriers such as biosafety, delivery efficiency, and lack of standardized catalytic performance metrics remain. This review critically addresses these challenges and highlights state-of-the-art nanozyme platforms, such as single-atom catalysts and cascade systems, which are leading the field toward clinical translation. Finally, it proposes strategic directions to bridge current knowledge gaps and advance nanozymes from bench to bedside, positioning them as next-generation catalytic platforms for personalized oncology.