Extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSC), hereinafter MSC-EVs, are already a great tool for researchers. Over the past decade, their use has expanded from basic research to preclinical and clinical phases. Scientists worldwide are increasingly using them as vehicles for therapies and as strategies for targeting specific cell types. Although the scientific community has immensely expanded knowledge on EVs and MSC-EVs, there are still several crucial aspects that need to be addressed before witnessing the unleash of EV into the clinical market. In this chapter, we will present a state-of-the-art overview of different technologies and approaches on how to functionalize and manipulate EVs to make them more effective in tissue targeting and drug delivery. We will also take into consideration some methodologies useful to protect EVs during their journey in the human body and to facilitate their internalization once that they reached their final destination.