Background Hepatic first-pass metabolism and poor therapeutic efficiency at targeted region are the endemic problems of new drug molecules. Thus, comprehensive research has been carried out on the novel vesicular drug delivery systems in nanotechnology from the last few years. These nano-carrier systems have developed to overcome the limitations that are associated with hepatic first-pass metabolism in conventional oral dosage forms and the barrier properties of the lipid bilayer in stratum corneum via transdermal drug delivery for improving the bioavailability of various drugs. Main body In recent years, several targeted vesicular drug delivery carriers are developing like liposomes, niosomes, proniosomes, transferosomes, ethosomes, and electrosomes. Among them, niosomes and proniosomes are to be better carriers to increase therapeutic efficiency and bioavailability by reducing the side effects and acting as a promising approach for transdermal drug delivery. Both are non-ionic surfactant-based vesicles and are amphiphilic. This article concisely reviews the possible mechanisms within niosomes and pronisomes to enhance transdermal drug delivery, types, composition, preparation techniques, characterizations, and its applications. Conclusion As per the researches done in the formulation of various nano-carrier systems through transdermal approach for the enhancement of bioavailability, it can be stated that the hepatic first pass metabolism can be reduced as well as therapeutic efficiency can be increased by many folds compared to their oral marketed formulations.