In this study, we have applied the simplified model, called the Ohta–Kawasaki model, to find the optimal process conditions at which the thickness of the PS residual layer was minimized. Prior to the optimization, we demonstrated that the simplified model not only has a reasonable accuracy, but also an extremely short calculation time. Then, we calibrated the model parameters with the cross-sectional TEM images, and minimized the thickness of the PS residual layer by varying the guide hole shape (i.e., hole diameter, height, and taper angle). Our simulation results showed that it is difficult to eliminate the entire PS residual layer by only varying the guide hole shape. Alternatively, by changing the affinity of the bottom surface from “PMMA-attractive” to “neutral,” we could obtain a relatively wide, defect-free (i.e., no PS residual layer) process window. The same effect on the neutral bottom surface was observed for the case with an elliptical guide hole. Since our simulations are computationally inexpensive and scalable, they may also be feasible for large-scale simulations such as the hotspot (i.e., defects) analysis over a large area.