A method of drug delivery that could provide control over medicine reaching the bloodstream for systemic circulation would be of immense importance. This work presents a comparative study of the temporal and spatial variation of drugs diffusing passively through two separate routes of human skin, namely intercellular (ICR) and sweat duct route (SDR). Analysis is carried out for two age groups (young < 40 years and old > 60 years of age). Governing equations based on Fick’s law for mass transfer has been solved numerically using an in-house developed code. The code has been validated thoroughly with numerical and experimental work from literature. Each skin route is modeled into three compartments sandwiched between donor and receiver compartment. To understand the role of diffusion and partition coefficient on drug permeation, four drugs, namely hydrocortisone, transcinnamic acid, caffeine, and benzoic acid, are considered. Drug diffusion rate is found greater through ICR as compared to SDR. Further, the amount of drugs diffusing through both routes increases with age. Desirable drug characteristic is inferred to be a lower value of partition coefficient and a higher value of diffusion coefficient. This study could lead to real-time assessment of medicines reaching the bloodstream and beyond.