Mortality worldwide continues to be driven by cancer rates through centuries. Even in the early stages of tumor cases, limitations of traditional tumor therapeutic methods include a lack of selectivity and drug resistance due to hypoxic tumor cells, leading to the requirement of developing efficient and localized therapeutic approaches. A promising therapeutic strategy has emerged: multimodal synergistic strategies that integrate multiple treatment methods, including chemodynamic, photodynamic, and photothermal therapy. The enzyme-mimetic properties of nanomaterials are highly attractive for nanomedicine, as they offer cost-effective catalytic platforms with enhanced stability and sustained catalytic activity across broader pH and temperature ranges compared with natural enzymes, including under the harsh conditions of the tumor microenvironment. In this context, combined manganese oxide and gold nanostructures are designed to develop multi-enzymatic reactions of Glucose Oxidase-, Peroxidase-, and Catalase-like activities for controlled reactive oxygen species generation for tumor therapy as a self-sustaining loop called cascade systems. While MnO2 is involved in catalytic reactions with having redox active and semiconductor features, localized heating and hot electrons created by the unique optical properties (localized plasmon surface resonance) of Au boost the catalytic activities. By exploiting these enzyme-mimetic activities, biodegradable multifunctional nanoparticles can be combined with plasmonic nanomaterials to establish an optimized synergistic therapeutic platform capable of enhancing catalytic performance and therapeutic efficacy within the tumor microenvironment.