Topical drug administration represents an effective therapeutic strategy for epithelial treatment, primarily due to its non-invasive characteristics. This study examines the pharmaceutical efficacy of liposomal nano-drugs across various human skin types, taking into account differences in body location and gender. Given the minimal velocity of interstitial fluid within the extracellular matrix, drug penetration predominantly occurs via chemical diffusion. A compartmental numerical model, grounded in the convection–diffusion–reaction equation, was developed to assess drug kinetics, encompassing processes from encapsulation breakdown to the binding of the parental drug with tissue proteins. The analysis incorporates the pharmacokinetic parameter of the area under the curve (AUC) to quantify drug accumulation within specific skin layers. Temporal AUC data reveal variations in drug distribution and accumulation across different tissues, underscoring the availability of systemic circulation for transdermal drug delivery. The liposomal encapsulation utilized in this study is pH-sensitive, and the pharmacokinetic parameters of the drugs are varied to facilitate ADME (absorption, distribution, metabolism, and excretion) analysis. Results demonstrate significant variations in drug performance based on body location and gender. Furthermore, the findings offer insights into optimizing external stimuli, such as release rates and initial doses, to enhance therapeutic efficacy. Numerical formulations were discretized using a finite difference approach to account for the linear geometry and layer-wise heterogeneity of human skin. A computational code was developed in MATLAB, implementing an iterative point-by-point solution strategy. This study provides a comprehensive framework for understanding and improving the transdermal delivery of nano-drugs.