Skin is the largest organ of human offering important pathway for drug delivery. Drug delivery through transdermal pathway have to penetrate through the skin tissue to realize absorption, thereinto, stratum corneum turns out to be the largest barrier to accomplish transdermal drug delivery. Owing to the specific interactions between nano-formulations and skin tissue, transdermal nanocarrier could provide advantages, such as improving skin penetrating efficiency, sustaining release, avoiding the first-pass effect, decreasing side effects, etc. The structures and components of nano-formulations play crucial roles in enhancing skin penetration. A better and more comprehensive understanding of the correlations between them is not only favorable for the design of novel transdermal nanocarrier, but also beneficial to establish safe, efficient and functional transdermal drug delivery system.