MXenzymes, a promising class of catalytic therapeutic material, offer great potential for tumor treatment, but they encounter significant obstacles due to suboptimal catalytic efficiency and kinetics in the tumor microenvironment (TME). Herein, this study draws inspiration from the electronic structure of transition metal vanadium, proposing the leverage of TME specific-features to induce structural transformations in sheet-like vanadium carbide MXenzymes (TVMz). These transformations trigger cascading catalytic reactions that amplify oxidative stress, thereby significantly enhancing multimodal tumor therapy. Specifically, the engineered HTVMz, coated with hyaluronic acid, exhibits good stability and generates a thermal effect under NIR-II laser irradiation. The thermal effect, combined with TME characteristics, facilities a structural transformation into ultra-small vanadium oxide nanozymes (VO