Smart micro/nanoparticles (MNPs) in stimulus-responsive drug and gene delivery systems have emerged as promising tools for targeted and controlled drug delivery. These MNPs can respond to various stimuli, including pH, redox, temperature, magnetic fields, light, and ultrasound, enabling precise drug release. The review highlights the development of smart MNPs tailored to specific stimuli, such as pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles, and light or ultrasound-sensitive particles. These MNPs are crucial for site-specific drug delivery, reducing side effects, and improving treatment efficacy. The review also discusses the challenges and future applications of these smart MNPs in pharmaceuticals, including their use in cancer therapy, drug delivery, and imaging. Thermo-responsive MNPs, such as poly(N-isopropylacrylamide) (PNIPAAm), are sensitive to temperature changes and can be used for controlled drug release. Magnetic-responsive MNPs, which respond to external magnetic fields, are effective for targeted drug delivery and hyperthermia. Electrical-responsive MNPs can be triggered by electric fields for sustained or on-demand drug release. Light-responsive MNPs, including those sensitive to near-infrared (NIR) light, offer non-invasive drug release with minimal tissue damage. These stimuli-responsive MNPs have shown potential in various applications, including cancer treatment, gene delivery, and tissue engineering. The review emphasizes the importance of understanding the underlying mechanisms of these MNPs to further advance their use in nanomedicine.Smart micro/nanoparticles (MNPs) in stimulus-responsive drug and gene delivery systems have emerged as promising tools for targeted and controlled drug delivery. These MNPs can respond to various stimuli, including pH, redox, temperature, magnetic fields, light, and ultrasound, enabling precise drug release. The review highlights the development of smart MNPs tailored to specific stimuli, such as pH-sensitive peptides and polymers, redox-responsive micelles and nanogels, thermo- or magnetic-responsive nanoparticles, and light or ultrasound-sensitive particles. These MNPs are crucial for site-specific drug delivery, reducing side effects, and improving treatment efficacy. The review also discusses the challenges and future applications of these smart MNPs in pharmaceuticals, including their use in cancer therapy, drug delivery, and imaging. Thermo-responsive MNPs, such as poly(N-isopropylacrylamide) (PNIPAAm), are sensitive to temperature changes and can be used for controlled drug release. Magnetic-responsive MNPs, which respond to external magnetic fields, are effective for targeted drug delivery and hyperthermia. Electrical-responsive MNPs can be triggered by electric fields for sustained or on-demand drug release. Light-responsive MNPs, including those sensitive to near-infrared (NIR) light, offer non-invasive drug release with minimal tissue damage. These stimuli-responsive MNPs have shown potential in various applications, including cancer treatment, gene delivery, and tissue engineering. The review emphasizes the importance of understanding the underlying mechanisms of these MNPs to further advance their use in nanomedicine.