Despite the advantages of transdermal drug delivery (TDD), which makes it a fast-growing area of research in pharmaceutics, numerous challenges affect their development, which limits exploring the full potential of this alternate drug delivery route. In trying to address one of these problems, it is strongly believed that the need for a sustainable skin alternative is paramount. Efforts made in an attempt to provide a sustainable alternative to employing skin in pharmaceutical analysis, by better utilising a polymer membrane, namely poly(dimethylsiloxane), also known as PDMS are discussed. Several combined properties of this polymer, which includes its relative stability in comparison with human skin, make it a good candidate for the replacement of skin. Modifications undertaken to this polymer membrane (to create an enhanced skin mimic for permeation analysis) are discussed and reviewed in this paper, including the improved ability to predict permeability for both hydrophobic and hydrophilic drugs. Optimisations related to studying TDD including limitations encountered are also documented and reviewed. It is hoped that such developments in this field will ultimately lead to researchers replacing skin with optimised polymer-based alternatives to predict transdermal drug delivery.