Ultrasound-based drug delivery is a transformative approach that enhances the efficacy and precision of therapeutic agents. It improves the delivery of drugs through diverse mechanisms including cavitations, acoustic streaming, sonoporation, and thermal effects. This method enables targeted delivery, reduces side effects, and offers versatile, noninvasive applications. This chapter discusses ultrasound technology fundamentals, including hyperthermia and acoustic streaming, which facilitate drug transport. Additionally, the chapter focuses on recent advancements including smart drug delivery systems like liposomes, polymers, and microbubbles that respond to ultrasound for modified release. Moreover, potential applications of ultrasound-mediated drug delivery systems for managing various diseases are also discussed. Further, challenges regarding safety, optimal ultrasound parameters, and delivery efficiency are briefed. Overall, ultrasound technology has the potential to revolutionize drug delivery, paving the way for innovative therapies. Further investigation is needed to address present constraints and optimize its clinical application.