Materdicine-augmented sonodynamic therapy has emerged as an efficient noninvasive strategy for cancer treatment by generating reactive oxygen species associated with the cavitation effect and sonosensitizers. However, semiconductor-based inorganic nanosonosensitizers have undesirable nondegradability, which can cause unsatisfactory therapeutic efficacy and potential toxicity. With the aim of overcoming this obstacle, in this study, Mo-assisted Te (MT) nanosonosensitizers with high oxidative degradation abilities are engineered for photoacoustic imaging (PA)-guided sonodynamic tumor nanotherapy. Intriguingly, the engineered MT nanosonosensitizers can generate abundant singlet oxygen under ultrasound irradiation to eradicate tumor cells, thereby demonstrating its ability to achieve high tumor growth inhibition rates. In particular, MT nanosonosensitizers exhibit oxidative degradation properties that guarantee desirable biocompatibility and potentiate clinical translation. Therefore, this study validates a paradigm for theoryoriented design of sonodynamic tumor nanotherapy.