Mesenchymal stem/stromal cells (MSCs) have shown promise in treating various diseases, but their clinical application faces challenges due to limited understanding of their pharmacokinetic (PK) and pharmacodynamic (PD) properties. MSCs can naturally migrate, localize, and proliferate in specific tissues, but their dynamic biodistribution, persistence, and fate in patients remain unclear. This review discusses the pharmacokinetic characteristics of MSCs, their key regulatory molecules, and detection methods, emphasizing the importance of understanding these factors for improving therapeutic efficacy and clinical outcomes. The review also highlights the need for advanced imaging and tracking technologies to address these challenges. MSCs are typically distinct from other cell therapies due to their "hit-and-run" mechanism, where they rapidly migrate to damaged tissues and release paracrine effectors, potentially leading to long-term effects. Secretome-derived bioproducts and extracellular vesicles retain the biological activity of MSCs and show similar therapeutic effects. The review outlines the key molecules involved in MSC motility, including selectins, integrins, chemokine receptors, and proteases. It also discusses the impact of different administration routes on MSC pharmacokinetics and the role of various chemokine receptors in MSC homing. The review highlights the importance of understanding MSC fate, including apoptosis, autophagy, differentiation, and phagocytosis, for assessing their safety and efficacy. MSCs are cleared from the body over time, with their persistence varying across studies. Understanding these factors is crucial for developing effective MSC therapies and improving their clinical application.Mesenchymal stem/stromal cells (MSCs) have shown promise in treating various diseases, but their clinical application faces challenges due to limited understanding of their pharmacokinetic (PK) and pharmacodynamic (PD) properties. MSCs can naturally migrate, localize, and proliferate in specific tissues, but their dynamic biodistribution, persistence, and fate in patients remain unclear. This review discusses the pharmacokinetic characteristics of MSCs, their key regulatory molecules, and detection methods, emphasizing the importance of understanding these factors for improving therapeutic efficacy and clinical outcomes. The review also highlights the need for advanced imaging and tracking technologies to address these challenges. MSCs are typically distinct from other cell therapies due to their "hit-and-run" mechanism, where they rapidly migrate to damaged tissues and release paracrine effectors, potentially leading to long-term effects. Secretome-derived bioproducts and extracellular vesicles retain the biological activity of MSCs and show similar therapeutic effects. The review outlines the key molecules involved in MSC motility, including selectins, integrins, chemokine receptors, and proteases. It also discusses the impact of different administration routes on MSC pharmacokinetics and the role of various chemokine receptors in MSC homing. The review highlights the importance of understanding MSC fate, including apoptosis, autophagy, differentiation, and phagocytosis, for assessing their safety and efficacy. MSCs are cleared from the body over time, with their persistence varying across studies. Understanding these factors is crucial for developing effective MSC therapies and improving their clinical application.