Nanozymes can improve reactive oxygen species (ROS)-based cancer therapies by targeting cancer cells' antioxidant defense mechanisms, particularly glutathione (GSH) depletion, to overcome ROS-resistant cancer cells. Nanozymes, innovative enzyme-mimetic nanomaterials, can generate ROS, alter the tumor microenvironment (TME), and synergize with photodynamic therapy (PDT), chemodynamic therapy (CDT), radiotherapy, and immunotherapy. This review shows how nanozymes catalyze ROS generation, selectively deplete GSH, and target cancer elimination, offering clear advantages over standard therapies. Nanozymes selectively target cancer cells' antioxidant defenses to improve PDT, CDT, and radiation therapies. To maximize nanozyme-based cancer treatment efficacy, biodistribution, biocompatibility, and tumor heterogeneity must be assessed. To improve cancer treatment, multifunctional, stimuli-responsive nanozymes and synergistic combination drugs should be developed.