Abstract

Abstract Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising therapy approach for deep‐seated tumors. However, the general or only utilization of SDT shows low efficiency and unsatisfactory treatment outcomes due to the complicated tumor microenvironment (TME) and SDT process. To circumvent the issues, three feasible approaches for enhancing SDT‐based therapeutic effects, including sonosensitizer optimization, strategies for conquering hypoxia TME, and combinational therapy are summarized, with a particular focus on the combination therapy of SDT with other therapy modalities, including chemodynamic therapy, photodynamic therapy, photothermal therapy, chemotherapy, starvation therapy, gas therapy, and immunotherapy. In the end, the current challenges in SDT‐based therapy on tumors are discussed and feasible approaches for enhanced therapeutic effects are provided. It is envisioned that this review will provide new insight into the strategic design of high‐efficiency sonosensitizer‐derived nanotheranostics, thereby augmenting SDT and accelerating the potential clinical transformation.