Sonodynamic therapy (SDT) is a novel therapeutic method, exhibiting deep penetration, good cell membrane permeability and free exposure to light capacity. However, the hypoxic tumor microenvironment and poor targeting of sonosensitizers limit the treatment efficiency of SDT. Therefore, it is crucial to construct sonosensitizer-based nanoplatforms to achieve a more comprehensive therapeutic effect. Herein, we briefly introduce three mechanisms based on the ultrasonic cavitation effect and summarize the unsolvable problems such as tumor hypoxia and insufficient targeting. Then, we conclude with the representative work and the promising strategies which are (1) transport of O₂ through nanocarriers, (2) utilization of the catalytic function of enzymes, such as catalase, to generate O₂in situ, and (3) improvement of targeting efficiency by targeting organelles, and coating them with biofilm materials. In addition, this research proposes solutions to the following challenges faced by using nanomaterials: (1) potential long-term toxicity in the body, (2) limited oxygen carrying capacity, (3) low targeting efficiency and precision, and (4) the unsatisfactory effect of single therapy.