Nanoparticle/microparticle-based drug delivery systems have significant advantages over traditional drug formulations, particularly in systemic (intravenous) applications. These systems can deliver therapeutics to areas that other delivery methods cannot reach, making them highly investigated in preclinical and clinical settings. This review highlights the diversity of nanoparticle types, their key advantages, and their potential in clinical care. It focuses on clinically approved nanoparticle systems, both for their current indications and in active clinical trials, while also discussing the biological, technological, and study design challenges that impact their clinical success. The review emphasizes the importance of addressing these challenges to ensure the effective translation of nanoparticle-based therapies into clinical practice.Nanoparticle/microparticle-based drug delivery systems have significant advantages over traditional drug formulations, particularly in systemic (intravenous) applications. These systems can deliver therapeutics to areas that other delivery methods cannot reach, making them highly investigated in preclinical and clinical settings. This review highlights the diversity of nanoparticle types, their key advantages, and their potential in clinical care. It focuses on clinically approved nanoparticle systems, both for their current indications and in active clinical trials, while also discussing the biological, technological, and study design challenges that impact their clinical success. The review emphasizes the importance of addressing these challenges to ensure the effective translation of nanoparticle-based therapies into clinical practice.