Transdermal drug delivery systems have been developed over the past several decades and now include patches for birth control, nicotine addiction, and pain relief. The local application of heat can increase the diffusion coefficient of the drug in the skin and result in faster delivery of the drug and shorter time to reach a steady state concentration of the drug. While this procedure is desirable for some systems where a faster dose will aid in alleviating pain and/or symptoms, it can also be a cause of concern for some drugs. Fentanyl, a chronic pain relief drug, can cause accidental death by overdose. We report herein an analysis of the effects of various heating situations on transdermal fentanyl delivery based upon a model developed using COMSOL Multiphysics. The utilization of such a model allows for the determination of situations which may be potentially dangerous for fentanyl drug users, and enables the development of usage guidelines and safety mechanisms for transdermal delivery systems. Using the computer model, the following cases were simulated: no applied heat, ThermaCare heat pad, fever, and heating blanket. The heating blanket and ThermaCare heat pad simulations showed the most dangerous increases in fentanyl blood concentration above no-heat levels: about 180% and 100%, respectively, over 30 hours; by contrast, the patient fever model reported a 40% increase in fentanyl blood concentration. These simulations demonstrate the dangers of fentanyl transdermal pain patches when skin temperature is increased, and can be used to develop better patient guidelines for patch use and to improve fentanyl transdermal systems. Lastly, this computer model may be used to model other transdermal drug delivery systems for the improvement of patient guidelines and/or the development of new systems, thus decreasing the need for experimentation on subjects.