In this work, the interfacial effect on the air resistance of the expanded polytetrafluoroethylene/polyphenylene sulfide (ePTFE/PPS) composite membrane was investigated experimentally and by numerical simulation. PPS fiber melting-caused diffusion, porosity reduction in laminating process, and turbulence effect of sudden changed airflow direction are confirmed to be the primary causes of the additional resistance, which occupy more than 40% of the total resistance. To eliminate the influence of PPS fiber melting-induced pore blocking in laminating process, the model modification parameter c and air permeability effective coefficient (σ) were introduced based on a digital image processing technology. A mathematical model was then established to predict and optimize the composite membrane. The predictions from the theoretical calculation were quantitatively in good agreement with the experimental measurements. It was found that profiled fiber with smaller intersection angle and diameter ratio can effectively decrease ~86% of IIR.