Improving drug permeability in the skin is one of the most important issues for designing new methods of transdermal drug delivery. Consequently, many techniques have been proposed to effectively deliver drugs across the stratum corneum. The microneedle is a new technology to enhance transdermal delivery of high-molecular-weight drugs. This technique combines the concepts of transdermal drug delivery across the skin with patches and hypodermic injections. The microneedles have been shown experimentally to increase the skin permeability by orders of magnitude in vitro for a range of drugs that differ in molecular size and weight. Recently, other questions appeared while using these microneedles, such as how to reduce needle diameters by which the hole is produced to be as small as possible to exclude bacteria and other foreign particles. Another issue is how to correlate the skin thickness and microneedle length with the skin permeability. In this work, we have developed an optimization framework for improving skin permeability to drugs by using microneedle arrays, which considers different classifications of skin thickness arising from different races, sex groups, ages, and anatomical regions. To know the optimum design of these microneedles, the effect of the microneedle geometry (e.g., number of microneedles, microneedle radius) on skin should be determined. In this work, the optimization algorithm is presented. The outcome of this work will be used to suggest optimum microneedle designs based on the parameters of interest.