With interest in non-invasiveness and safety in cancer treatment, sonodynamic therapy (SDT) has emerged as a promising alternative to conventional cancer therapies. SDT offers safety and cost-effectiveness and exhibits a broad application range that is superior to photodynamic therapy. However, the insufficient reactive oxygen species (ROS) production of current sonosensitizers has hindered its clinical application to date. In this review, the ROS-generation mechanism in SDT and the limitations of current sonosensitizers are briefly reviewed. Also, highlighted are recent nanomaterial-based SDT strategies to improve the efficiency of sonosensitizers, amplify oxidative stress, and elicit antitumor immunity.