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The Stimulator of Interferon Genes (STING) pathway is implicated in the innate immune response and is important in both oncogenesis and cancer treatment. Specifically, activation of the cytosolic DNA sensor STING in antigen-presenting cells (APCs) induces a type I interferon response and cytokine production that facilitates antitumor immune therapy. However, use of STING agonists (STINGa) as a cancer therapeutic has been limited by unfavorable pharmacological properties and targeting inefficiency due to rapid clearance and limited uptake into the cytosol. Exosomes, a class of extracellular vesicles shed by all cells are under consideration for their use as effective carriers of drugs owing to their innate ability to be taken up by cells and their biocompatibility for optimal drug biodistribution. Therefore, we engineered exosomes to deliver the STING agonist cyclic GMP-AMP (iExo STINGa ), to exploit their favorable pharmacokinetics and pharmacodynamics. Selective targeting of the STING pathway in APCs with iExo STINGa was associated with superior potency compared with STINGa alone in suppressing B16F10 tumor growth. Moreover, iExo STINGa showed superior uptake of STINGa into dendritic cells compared with STINGa alone, which led to increased accumulation of activated CD8 + T-cells and an antitumor immune response. Our study highlights the potential of exosomes in general, and iExo STINGa specifically, in enhancing cancer therapy outcomes., Competing Interests: Conflict of interest V. S. L. is a paid consultant for Codiak Biosciences. MD Anderson Cancer Center and R. K. hold patents in the area of exosome biology (unrelated to the topic of this publication) and are licensed to Codiak Biosciences Inc. MD Anderson Cancer Center and R. K. are stock equity holders in Codiak Biosciences Inc. R. K. is a consultant and a scientific advisor of Codiak Biosciences Inc., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)