Sonodynamic therapy (SDT) is an emerging treatment method. In comparison with photodynamic therapy (PDT), SDT exhibits deep penetration, high cell membrane permeability, and free exposure to light capacity. Unfortunately, owing to inappropriate ultrasound parameter selection, poor targeting of sonosensitizers, and the complex tumor environment, SDT is frequently ineffective. In this review, we describe the approaches for selecting ultrasound parameters and how to develop sonosensitizers to increase targeting and improve adverse tumor microenvironments. Furthermore, the potential of combining SDT with other treatment methods, such as chemotherapy, chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy, is discussed to further increase the treatment efficiency of SDT.