Topical and transdermal delivery has been studied over last decades and it presents advantages for the treatment of several disorders, macromolecules delivery and vaccination. The greatest challenge is to overcome the stratum corneum (SC) barrier. Compared to traditional topical formulation strategies, nano /microsystems offer advantages such as increased stability, increased loading dose, coverage of undesired colors, reduced toxicity and prolonged release of active agents. However, there are no conclusive studies demonstrating the ability of such systems to penetrate the skin in relevant therapeutic amounts. The use of physical methods holds great promise for enhancing skin permeation through the SC and for targeting hair follicles. This review discusses the characteristics and feasibility of using a dual approach employing the application of physical methods of permeation enhancement to enable the topical or transdermal delivery of drug-loaded nano/microsystems.