A multiscale modeling of the anisotropic slip phenomenon for gas flows is presented in a tree-step approach: determination of the gas–wall potential, simulation and modeling of the gas–wall collisions, simulation and modeling of the anisotropic slip effects. The density functional theory (DFT) is used to examine the interaction between the Pt–Ar gas–wall couple. This potential is then passed into molecular dynamics (MD) simulations of beam scattering experiments in order to calculate accommodation coefficients. These coefficients enter in an effective gas–wall interaction model, which is the base of efficient MD simulations of gas flows between anisotropic surfaces. The slip effects are quantified numerically and compared with simplified theoretical models derived in this paper. The paper demonstrates that the DFT potential is in good agreement with empirical potentials and that an extension of the Maxwell model can describe anisotropic slip effects due to surface roughness, provided that two tangential accommodation parameters are introduced. MD data show excellent agreement with the tensorial slip theory, except at large Kundsen numbers (for example, Kn 0.2) and with an analytical expression which predicts the ratio between transverse and longitudinal slip velocity components.