AbstractExtracellular vesicles (EVs) are transport vesicles secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as “messengers” in intercellular and inter‐organismal communication, in both normal and pathological processes. EVs, as natural nanocarriers, can deliver bioactivators in therapy with their endogenous transport properties. This review article describes the engineering EVs of sources, isolation method, cargo loading, boosting approach, and adjustable targeting of EVs. Furthermore, the review summarizes the recent progress made in EV‐based delivery systems applications, including cancer, cardiovascular diseases, liver, kidney, nervous system diseases, and COVID‐19 and emphasizes the obstacles and challenges of EV‐based therapies and possible strategies.