Extracellular Vesicles (EVs) are important cell communication mediators that are being explored to modulate inflammation and immune response in several different contexts, from anti-cancer immunotherapies to regenerative medicine. The current chapter encompasses recent evidence supporting the immunomodulatory roles mediated by EVs in the context of cancer and tissue repair/regeneration. The EV-mediated cross-talk between cancer and immune cells, and their contribution to the tumour outcome including metastasis formation are discussed. Also, their impact on the response to conventional therapies and contribution of EVs for future therapies are addressed. On the other hand, the potential of EVs, particularly those from mesenchymal stem/stromal cells, as therapeutic tools in immunomodulation for improved tissue repair and regeneration is examined. Examples are drawn particularly from injuries/diseases of the musculoskeletal and cardiovascular systems, and in kidney and lung fibrosis. Moreover, the EVs' contributions to extracellular matrix deposition and remodelling in cancer and tissue repair/regeneration, are also addressed. The chapter concludes with a brief discussion of aspects that still require research and development, in order for the fulfilment of the great promise of EV-based therapeutics.