Automotive metal door panels and nonmetallic seals have complicated nonlinear interactions in their narrow mating sections, leading to non-uniform compression and complicating the sound transmission mechanism. Therefore, a new sound transmission modeling methodology and numerical analysis is developed for a refined sealing system by considering the geometrical boundaries and the non-uniform compression load. Nonlinear analysis is performed to obtain the geometrical parameters of the deformed seal, which are later input to the subsequent numerical acoustic model, by varying the compression ratios at different door locations under quantified nonlinear metal–seal interaction boundary conditions. A numerical prediction model of the sound transmission loss is constructed considering the deformed seal geometry using a double-wall-panel sound transmission model. Finite-element analysis and an infinite-element method are combined. Sound transmission loss experiments are conducted by varying the compression ratios of the seal. Experimental results are in good agreement with the numerical analysis. Furthermore, the sound transmission loss of the incident sound source with respect to a wide range of frequencies is numerically predicted for different compression magnitudes and directions using the verified methodology. This shows that the presented model and numerical methodology is valuable for optimizing the sound transmission loss performance of automotive door seals.