A novel optimization approach is proposed for the development of the body-in-white model of a hatchback car based on the effective independence–weighted average acceleration amplitude method and the modal assurance criterion. By employing this optimization method, not only are the modal frequency and the mode shape identified more accurately, but also the experimental efficiency is significantly improved. According to the level of concern of the vibration mode, weighted factors are given to the modal features in order to make the sensor arrangement more efficient and reasonable. The target parameters are obtained by a sensitivity analysis of the design parameters of the hatchback car and an optimization is carried out. An acoustic–structural coupled model is developed on the basis of the optimized body-in-white model and used for prediction of the interior structure-borne noise of the hatchback car. The predicted results of the sound pressure level show good agreement with the experimental data, particularly at the frequencies concerned. By using the multi-position multi-frequency method, the mean acoustic contribution coefficient is proposed, and the panels with significant influence on the interior noise are identified. Accordingly, some modifications of the car body are made by using damping material. As a result, the interior noise decreases totally in the range from 10 Hz to 60 Hz. Some significant reductions are obtained at 23.34 Hz and 46.68 Hz, namely 4.1 dB(A) and 2.5 dB(A) at the position of the driver’s right ear and 4.6 dB(A) and 3.5 dB(A) at the middle of the rear seat.