The emergence of lipid nanovesicles (LNVs), like liposomes, transferosomes, and ethosomes, strengthens transdermal drug delivery. The composition of lipid vesicles is similar to that of skin, so these can easily penetrate through the skin. Modifications in the design of lipid vesicles help enhance skin permeation; therefore, dose reduction is possible. Ultradeformable vesicles are superior to conventional lipid vesicles because of their better stability. Various methods used to prepare LNVs are the classical cold method, ethanol injection method, ether injection method, and film hydration method. The method of preparation is crucial because it drastically affects the characteristics of vesicles. The vesicles are evaluated for their physicochemical and biological properties. Since vesicular systems are more susceptible to physical, chemical, and biological degradation, their stability is critical and challenging. The transdermal applications of LNVs spread across all areas like antifungal, anti-inflammatory, and anticancer drugs and the delivery of proteins and peptides.