The exosome is a naturally derived nanostructured lipid vesicle that ranges from 40-100 nm in size and is utilized to transport drugs, and biological macromolecules, including therapeutic RNA and proteins. It is a membrane vesicle actively released by cells to transport cellular components with a purpose for biological events. The conventional isolation technique has several drawbacks, including low integrity, low purity, long processing time, and sample preparation. Therefore, microfluidic technologies are more widely accepted for the isolation of pure exosomes, but due to cost and expertise requirements, this technology is also facing challenges. The bioconjugation of small and macro-molecules to the surface of exosomes is a very interesting and emerging approach for achieving the specific target, therapeutic purpose, in vivo imaging, and many more. Although emerging strategies resolve a few challenges, exosomes are still unexplored complex nano-vesicles with excellent properties. This review has briefly elaborated on contemporary isolation techniques and loading approaches. We have also discussed the surface-modified exosomes by different conjugation methods and their applications as targeted drug delivery vesicles. The challenges associated with the exosomes, patents, and clinical investigations are the main highlight of this review.