Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (HO) levels in the tumor microenvironment (TME) poses challenges. Herein, an HO self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO) (denoted as ZnO@Pt). ZnO releases HO in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from HO while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn released from ZnO interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn release, downregulating ATP and NAD levels. In vivo assessment of anticancer effects showed that ZnO@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of HO self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.