<p>Extracellular vesicles (EVs), nanoscale membranous structures secreted by cells, have gradually evolved from being passive communication vehicles and could now contribute to the development of engineerable theranostic nanoplatforms. Among these, tissue-derived extracellular vesicles (Ti-EVs) have demonstrated the potential for higher yields and may better reflect the physiological or pathological state of the tissue microenvironment compared to cell-culture counterparts. These advantages may make Ti-EVs potentially valuable tools for studying disease mechanisms and developing targeted therapies. This review provides a comprehensive overview of Ti-EVs, including their isolation, characterization, and biological functions in various diseases. By summarizing the latest research and technological advances, we evaluate the potential of Ti-EVs to serve as modulators of disease progression, and discuss the challenges in their clinical applications.</p> Graphical abstract <p></p>