Ultrasound is one of the safest and most advanced medical imaging technologies that is widely used in clinical practice. Ultrasound microbubbles, traditionally used for contrast-enhanced imaging, are increasingly applied in Ultrasound-targeted Microbubble Destruction (UTMD) technology which enhances tissue and cell membrane permeability through cavitation and sonoporation, to result in a promising therapeutic gene/drug delivery strategy. Here, we review recent developments in the application of UTMD-mediated gene and drug delivery in the diagnosis and treatment of tumors, including the concept, mechanism of action, clinical application status, and advantages of UTMD. Furthermore, the future perspectives that should be paid more attention to in this field are prospected.