Human skin, the largest external organ of the body, provides a selective barrier to therapeutics applied topically. The molecules having specific chemical and physical properties can only penetrate the deeper layer of the skin. However, the lag time for reaching a steady state in the deeper layer is generally of the order of hours. In order to deliver higher molecular weight, charged and hydrophilic therapeutics in the deeper layer, skin barrier must be breached out. Electroporation is one of the methods used to breach the skin barrier for enhancement of drug permeation and reduction of lag time. However, underlying mechanism responsible for enhancement of drug permeation is not well understood. In this study, multiscale model of skin electroporation is developed by connecting molecular phenomena to macroscopic model. At atomic scale, molecular dynamics simulations of lipid matrix of human stratum corneum were performed under the influence of external electric field. The pores get formed during the electroporation process and the transport properties (diffusivity) of drug molecules are computed. The diffusion coefficient obtained during electroporation was found to be higher than the passive diffusion. However, this alone could not explain the multifold increase in the drug flux on application of electric field as observed in the experiments. Hence, a finite element method (FEM) model of skin stratum corneum is also developed. The release of fentanyl through this model is compared with available experimental results. Both experimental and simulated results of pore formation on application of electric field and many folds increase in drug flux are comparable. Once validated, the framework was used for design of skin electroporation experiments (in-silico) by changing the electric pulse parameters such as voltage, pulse duration and number of pulses. This multiscale modelling framework provides valuable insight at molecular and macroscopic level to design the electroporation experiments. The framework can be utilized as a design tool for skin electroporation applications.