Conventional formulations for topical administration of drugs have certain drawbacks like poor adherence to skin, poor permeability and compromised patient compliance. Topical film forming systems are such developing drug delivery systems meant for topical application to the skin, which adhere to the body, forming a thin transparent film and provide delivery of the active substances to the body tissue for longer duration. The objective of the present research work was to formulate and evaluate spray-based film forming systems for fungal and bacterial infections. The formulation was prepared by addition of film-forming polymers to the solvent system followed by addition of plasticizer and drug. Two different Film forming spray solutions were prepared of Clotrimazole and Mupirocin calcium along with ethyl cellulose and eudragit RS 100 as film formers, PEG 400 and PEG 5000 as plasticizer and ethanol, acetone as the solvent mixture. Optimization was done by 32 factorial design using Design expert 13 software. The optimized formulations were evaluated for various parameters like viscosity, drying time, spray angle, film formation time, drug release, anti-microbial activity, pH and water washability. Film forming systems will provide a better platform for topical delivery against various skin infections with benefits like controlled release, reduced dosing, water resistance, curbing further infection, reduced risk of wiping out, contact free application, etc as compared to the conventional semisolid dosage forms