A new methodology for modeling minority carriers diffusion in Smart Power ICs substrate using standard circuit simulators has been proposed by EPFL. For this purpose, a parasitic substrate network consisting of lumped elements is extracted from the circuit layout following a given substrate meshing strategy. In this work Design of Experiments (DOE) techniques are used to run a limited number of simulations to evaluate the influence of the meshing on the accuracy of the EPFL Substrate Model when compared to finite element simulations. A two-dimensional case study on a parasitic lateral bipolar is then proposed with both spice-like and finite element simulation results for the minority carriers diffusion. A linear model is developed to estimate the most important geometrical domains influencing the accuracy of the studied model.