Recent considerable technological advances in ultrasound‐based treatment modality provides a magnificent prospect for scientific communities to conquer the related diseases, which is featured with remarkable tissue penetration, non‐invasive and non‐thermal characteristics. As one of the critical elements that influences treatment outcomes, titanium (Ti)‐based sonosensitizers with distinct physicochemical properties and exceptional sonodynamic efficiency have been applied extensively in the field of nanomedical applications. To date, a myriad of methodologies has been designed to manipulate the sonodynamic performance of titanium‐involved nanomedicine and further enhance the productivity of reactive oxygen species for disease treatments. In this comprehensive review, the sonocatalytic optimization of diversified Ti‐based nanoplatforms, including defect engineering, plasmon resonance modulation, heterojunction, modulating tumor microenvironment, as well as the development of synergistic therapeutic modalities is mainly focused. The state‐of‐the‐art Ti‐based nanoplatforms ranging from preparation process to the extensive medical applications are summarized and highlighted, with the goal of elaborating on future research prospects and providing a perspective on the bench‐to‐beside translation of these sonocatalytic optimization tactics. Furthermore, to spur further technological advancements in nanomedicine, the difficulties currently faced and the direction of sonocatalytic optimization of Ti‐based therapeutic nanomedicine are proposed and outlooked.