Sarcoma is a group of rare and heterogeneous mesenchymal tumors, prone to late diagnosis and poor prognosis. Exosomes are cell-derived small extracellular vesicles found in most body fluids and contain nucleic acids, proteins, lipids, and other molecules. Qualitative and quantitative changes of exosomes and the contents are associated with sarcoma progression, exhibiting their potential as biomarkers. Exosomes possess the capacity of evading immune responses, bioactivity for trafficking, tumor tropism, and lesion residence. Thus, exosomes could be engineered as tumor-specific vehicles in drugs and RNA delivery systems. Exosomes might also serve as therapeutic targets in targeted therapy and immunotherapy and be involved in chemotherapy resistance. Here, we provide a comprehensive summary of exosome applications in liquid biopsy-based diagnosis and explore their implications in the delivery system, targeted therapy, and chemotherapy resistance of sarcoma. Moreover, challenges in exosome clinical applications are raised and some future research directions are proposed.Copyright © 2022 Elsevier B.V. All rights reserved.