A finite element-based acoustic-structure interaction analysis tool has been developed to determine the noise transmission loss characteristics of door seal systems. This tool has been applied to determine the effects of the individual parameters, such as seal material density, seal constitutive model, separation distance between seal layers, external cavity shape, and seal prestress field, on noise transmission characteristics. Our findings indicate that the external and internal cavity shapes, seal material density, and deformed seal geometry are the key factors affecting the noise transmission through seal system. Increasing seal material density decreases the resonance frequencies and increases the overall sound transmission loss. Changing the separation distance between seal layers changes the sound transmission characteristics without changing the compression load deflection behavior of the seal system. Moving the resonant frequencies to desired frequency regions, we can reduce seal system contribution to the vehicle interior noise level. The nature of the resonance frequencies of this coupled system have also been determined. This analysis tool was applied to determine the noise transmission characteristics of a vehicle door seal system, and the seal system contribution to the vehicle interior noise level.