Extracellular vesicles (EVs) are increasingly being recognised for their therapeutic potential. EVs naturally contain various cargo including nucleic acids, proteins, and other biological material, and can have intrinsic anti-inflammatory and pro-angiogenic properties. Furthermore, EVs can be customised in order to enhance their natural therapeutic abilities. There are several strategies for customising EVs, including both surface and luminal EV modifications. Surface alterations may enable the targeting of EVs to particular cell types or tissues to enhance their ability to directly transfer cargo and to modify pathological states with reduced off-target effects and increased efficiency. In addition to surface modifications, there are currently several strategies that enable loading of cargo, such as small molecule drugs, nucleic acids, and proteins into EVs. Incubation, electroporation, transfection and sonication of EVs are some examples of techniques that have been reported for the loading of cargo into EVs. The techniques to modify the surface and load cargo into the lumen of EVs are still being established, in addition to the analytics of EV cargo to ensure loading and modification was successful. Here we review the current knowledge of EV targeting, loading, and delivery mechanisms, and in doing so outline their potential as therapeutics. VivaZome’s approach for customising EVs for treating traumatic brain injury and retinal degeneration will be highlighted. Further understanding the techniques and mechanisms that can be used to modify EVs will contribute to our ability to develop EV therapeutics with specific targeting and efficiency in order to develop effective therapeutics for many diseases.