Sonodynamic therapy (SDT) is a promising non-invasive therapeutic modality. Compared to photo-inspired therapy, SDT provides many opportunities and benefits, including deeper tissue penetration, high precision, less side effects, and good patient compliance. Thanks to the facile engineerable nature of nanotechnology, nanoparticles-based sonosensitizers exhibit predominant advantages, such as increased SDT efficacy, binding avidity, and targeting specificity. This review aims to summarize the possible mechanisms of SDT, which can be expected to provide the theoretical basis for SDT development in the future. We also extensively discuss nanoparticle-assisted sonosensitizers to enhance the outcome of SDT. Additionally, we focus on the potential strategy of combinational SDT with other therapeutic modalities and discuss the limitations and challenges of SDT toward clinical applications.