In situ film-forming systems (FFS) are attractive drug delivery systems employed for the topical administration of drugs. They are transparent and have high substantivity and improved cosmetic attributes. Two types of polymeric materials, methyl methacrylate and cellulosic derivates, were employed for the topical delivery of mometasone furoate. A previous screening of polymers and plasticizers was performed to select the best candidates based on cosmetic characteristics. Water vapor permeability determines the occlusive profile, and it has been observed that it depends on the polymer type. The rheological, bioadhesion, and mechanical properties of the films revealed that the best candidates were Eudragit S100 and HPMC films. These polymers also exhibited the slowest drug release and limited permeation across the skin, with no alteration in the microstructure of the skin layers after diffusion experiments. Both FFS were adequate to improve patient compliance with treatment due to the cosmetic attractiveness and a potential reduction in administration frequency. They also potentially allow for administration to high-friction areas and the face.