Medication nonadherence results in avoidable symptom exacerbations and hospitalization, causing thousands of deaths and billions of dollars in healthcare costs annually. Although pharmacological therapies are present for chronic diseases, lengthy and complicated medication regimens often have high rates of nonadherence. Transdermal drug delivery is a potential method of reducing medication nonadherence as it allows for long-course medication regimens to be simplified to a one-time epidermal patch. We have engineered a transdermal drug delivery system on a customizable platform to longitudinally deliver a wide variety of soluble small-molecule drugs. As a proof of concept, we have chosen to administer long-course corticosteroids for chronic inflammatory disease via epidermal patch. A drug-in-adhesive matrix consisting of the drug, adhesive, solvents, and penetration enhancers, was cured onto a fluoropolymer release liner. The transdermal drug delivery system has an integrated tapering mechanism to avoid end-of-course steroid dependence and can incorporate other small-molecule medications required for cases of polypharmacy. To date, there have been no successful attempts to develop long-term steroid patches for systemic delivery, which may be attributed to issues with patch adhesion and skin irritation over extended periods of time. We have analyzed such challenges and have designed a proof of concept system to overcome these obstacles in order to provide patients with a simple, inexpensive, and effective solution to complicated and long-term treatment regimens.