External-field mediated transdermal drug delivery is a new alternative to oral delivery and hypodermic injections. This method allows patients to receive treatments via a drug-infused patch applied to the skin and offers continuous release of drug for up to a week. It is also relatively inexpensive compared to regular treatments. In our design, ultrasound and an applied electric field are used to increase the rate of drug diffusion and propagation from the patch into and across the skin. Previous research has shown that the application of ultrasound results in higher rates of transdermal transport by increasing the permeability of the stratum corneum. This permeabilization can be so great that the patch or drug reservoir itself becomes the most significant barrier to the overall transdermal drug transport. An applied voltage has been shown to be capable of creating a driving force for transport that counteracts this effect. In this project, we combined the effects of applied voltage and ultrasound in order to model the transdermal transport of insulin from a methyl-cellulose hydrogel through the skin. Because the typical drug-delivery patch is circular, we modeled the problem in a 2Daxisymmetric geometry. Next, we determined the effects of intensity and voltage on the average insulin concentration in the skin. To do this, we conducted a sensitivity analysis by varying the applied voltages and intensities on the hydrogel and calculating the corresponding average insulin concentration in the skin at a specific time point. Finally, by using an objective function, we maximized the flux of insulin through the skin while minimizing patient discomfort. The iontophoretic and sonophoretic aspects of our model were validated individually through comparison with experimental data. We found that voltage and intensity from ultrasound combined provide the greatest increase in insulin transport through the skin. An intensity of 1 kW/m2 in conjunction with an applied voltage of -2 V resulted in the optimum insulin flux through the skin while maintaining minimal patient discomfort. The optimal intensity was found to be at the lower end of the range of experimentally and clinically utilized values. This suggests that higher intensities may contribute unnecessary heating without significantly enhancing insulin transport through the skin. Based on our optimization results, it can be seen that transdermal delivery of insulin through the skin is efficient when coupled with ultrasound and applied voltage. Our results show that with the application of sonophoresis and iontophoresis, insulin is effectively able to diffuse through the skin into the bloodstream. Our optimization also shows that this type of insulin delivery would cause minimal discomfort or skin damage. This suggests that transdermal delivery of insulin through the skin is a promising treatment for patients with diabetes.