Ultrasound-responsive microbubbles and nanodroplets are promising agents for targeted drug delivery, enhancing cell permeability and facilitating drug absorption. This review discusses their drug delivery process, focusing on their mechanical response to ultrasound and the resulting physical and biological effects on cells. It also covers their pre-clinical and clinical implementation, highlighting challenges in translating them to clinical use. Microbubbles and nanodroplets are fabricated using various methods, including amalgamation and tip-sonication, with microbubbles typically having a diameter of less than 10 μm to avoid vascular blockage. They are functionalized with various ligands and drugs to target specific tissues and enhance drug delivery. The size of these agents significantly affects their behavior under ultrasound, with microbubbles resonating at specific frequencies and nanodroplets having longer circulation times due to their smaller size. The acoustic response of microbubbles and nanodroplets is influenced by factors such as shell composition, size, and surrounding medium. Ultrasound causes microbubbles to oscillate, leading to mechanical stress on cells and enhancing drug permeability. Nanodroplets can be vaporized into bubbles, increasing vascular permeability and enabling targeted drug delivery. However, the use of nanodroplets requires careful control of acoustic pressure to avoid unintended effects. The delivery of these agents involves intravenous injection, where they circulate in the bloodstream and are eventually cleared by the immune system. The EPR effect allows nanocarriers to accumulate in tumors, enhancing drug delivery. However, the effectiveness of this effect varies among different tumor types and is limited by the size and properties of the agents. The acoustic response of microbubbles is governed by the Rayleigh–Plesset equation, which describes their radial motion under ultrasound. The response of coated bubbles is influenced by shell properties such as dilatational modulus and viscosity. Variability in these properties can affect the bubble's response to ultrasound, with shell viscosity being a key factor in clinical settings. The review highlights the importance of understanding the acoustic response of microbubbles and nanodroplets to optimize their use in targeted drug delivery. It emphasizes the need for further research to improve their clinical translation and address challenges such as controlling acoustic pressure and ensuring the stability of the agents. The potential of these agents in drug delivery is significant, with applications in various therapeutic areas including the central nervous system, cardiovascular system, and solid tumors.Ultrasound-responsive microbubbles and nanodroplets are promising agents for targeted drug delivery, enhancing cell permeability and facilitating drug absorption. This review discusses their drug delivery process, focusing on their mechanical response to ultrasound and the resulting physical and biological effects on cells. It also covers their pre-clinical and clinical implementation, highlighting challenges in translating them to clinical use. Microbubbles and nanodroplets are fabricated using various methods, including amalgamation and tip-sonication, with microbubbles typically having a diameter of less than 10 μm to avoid vascular blockage. They are functionalized with various ligands and drugs to target specific tissues and enhance drug delivery. The size of these agents significantly affects their behavior under ultrasound, with microbubbles resonating at specific frequencies and nanodroplets having longer circulation times due to their smaller size. The acoustic response of microbubbles and nanodroplets is influenced by factors such as shell composition, size, and surrounding medium. Ultrasound causes microbubbles to oscillate, leading to mechanical stress on cells and enhancing drug permeability. Nanodroplets can be vaporized into bubbles, increasing vascular permeability and enabling targeted drug delivery. However, the use of nanodroplets requires careful control of acoustic pressure to avoid unintended effects. The delivery of these agents involves intravenous injection, where they circulate in the bloodstream and are eventually cleared by the immune system. The EPR effect allows nanocarriers to accumulate in tumors, enhancing drug delivery. However, the effectiveness of this effect varies among different tumor types and is limited by the size and properties of the agents. The acoustic response of microbubbles is governed by the Rayleigh–Plesset equation, which describes their radial motion under ultrasound. The response of coated bubbles is influenced by shell properties such as dilatational modulus and viscosity. Variability in these properties can affect the bubble's response to ultrasound, with shell viscosity being a key factor in clinical settings. The review highlights the importance of understanding the acoustic response of microbubbles and nanodroplets to optimize their use in targeted drug delivery. It emphasizes the need for further research to improve their clinical translation and address challenges such as controlling acoustic pressure and ensuring the stability of the agents. The potential of these agents in drug delivery is significant, with applications in various therapeutic areas including the central nervous system, cardiovascular system, and solid tumors.