Transdermal drug delivery systems (TDDS), commonly refered to as "patches", present a nonintrusive technique to provide medication without the need for invasive procedures. These products adhere to the skin and gradually release a specific dosage of medicine at a defined rate into the bloodstream. Compared with other methods of drug delivery, TDDS offer benefits such as reduced invasiveness, convenience for patients, and avoidance of the metabolic processes that occur when drugs are orally consumed. Throughout time, TDDS have been used to provide medications for various medical conditions (such as nicotine, fentanyl, nitroglycerin, and clonidine), and their potential for delivering biologics is currently being explored. This review investigates the current literature on the drug delivery efficacy of medical TDDS through the transdermal route. Additionally, the review addresses potential risks and failure modes associated with TDDS design and development as well as strategies for mitigating such risks. A thorough understanding of failure modes provides a blueprint to mitigate failure and produce high-quality efficacious therapeutics.