The advent of acoustically responsive nanodrugs that are specifically optimized for sonodynamic therapy (SDT) is a novel approach for clinical applications. Examining the therapeutic applications of sono-responsive drug delivery systems, understanding their dynamic response to acoustic stimuli, and their crucial role in enhancing targeted drug delivery are intriguing issues for current cancer treatment. Specifically, the suggested review covers SDT, a modality that enhances the cytotoxic activity of specific compounds (sonosensitizers) using ultrasound (US). Notably, SDT offers significant advantages in cancer treatment by utilizing US energy to precisely target and activate sonosensitizers toward deep-seated malignant sites. The potential mechanisms underlying SDT involve the generation of radicals from sonosensitizers, physical disruption of cell membranes, and enhanced drug transport into cells via US-assisted sonoporation. In particular, SDT is emerging as a promising modality for noninvasive, site-directed elimination of solid tumors. Given the complexity and diversity of tumors, many studies have explored the integration of SDT with other treatments to enhance the overall efficacy. This trend has paved the way for SDT-based multimodal synergistic cancer therapies, including sonophototherapy, sonoimmunotherapy, and sonochemotherapy. Representative studies of these multimodal approaches are comprehensively presented, with a detailed discussion of their underlying mechanisms. Additionally, the application of audible sound waves in biological systems is explored, highlighting their potential to influence cellular processes and enhance therapeutic outcomes. Audible sound waves can modulate enzyme activities and affect cell behavior, providing novel avenues for the use of sound-based techniques in medical applications. This review highlights the current challenges and prospects in the development of SDT-based nanomedicines in this rapidly evolving research field. The anticipated growth of this SDT-based therapeutic approach promises to significantly improve the precision of cancer treatment.