The article explores the dynamic interplay between autophagy and exosome formation, highlighting their roles in cellular communication and stress response. Exosomes, initially recognized for waste disposal, have emerged as key intercellular messengers with therapeutic and diagnostic potential. Autophagy, beyond its traditional role in waste removal, regulates intracellular communication pathways and contributes to a unique autophagy-dependent secretome. Secretory autophagy, triggered by stress stimuli, releases proteins involved in inflammation, including leaderless proteins that bypass the conventional endoplasmic reticulum-Golgi pathway. The convergence of exosome biogenesis and autophagy is exemplified by amphisomes, vesicles that integrate autophagic and endosomal pathways. Regulatory proteins like mTORC1 play a crucial role in both pathways, making them potential therapeutic targets for altering cellular secretion profiles. The review discusses the complex interplay between autophagy and exosome formation, emphasizing the potential to influence the secretome composition. While exosome secretion and cytokine preconditioning are well-established in regenerative medicine, the strategic manipulation of autophagy remains underexplored, presenting a promising but uncharted therapeutic landscape.The article explores the dynamic interplay between autophagy and exosome formation, highlighting their roles in cellular communication and stress response. Exosomes, initially recognized for waste disposal, have emerged as key intercellular messengers with therapeutic and diagnostic potential. Autophagy, beyond its traditional role in waste removal, regulates intracellular communication pathways and contributes to a unique autophagy-dependent secretome. Secretory autophagy, triggered by stress stimuli, releases proteins involved in inflammation, including leaderless proteins that bypass the conventional endoplasmic reticulum-Golgi pathway. The convergence of exosome biogenesis and autophagy is exemplified by amphisomes, vesicles that integrate autophagic and endosomal pathways. Regulatory proteins like mTORC1 play a crucial role in both pathways, making them potential therapeutic targets for altering cellular secretion profiles. The review discusses the complex interplay between autophagy and exosome formation, emphasizing the potential to influence the secretome composition. While exosome secretion and cytokine preconditioning are well-established in regenerative medicine, the strategic manipulation of autophagy remains underexplored, presenting a promising but uncharted therapeutic landscape.