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The present work is concerned with the objective of developing a process for practical multi-disciplinary design optimization (MDO). The main goal adopted here is to minimize the weight of a vehicle body structure meeting NVH (Noise, Vibration and Harshness), durability, and crash safety targets. Initially, for simplicity a square tube is taken for the study. The design variables considered in the study are width, thickness and yield strength of the tube. Using the Response Surface Method (RSM) and the Design Of Experiments (DOE) technique, second order polynomial response surfaces are generated for prediction of the structural performance parameters such as lowest modal frequency, fatigue life, and peak deceleration value. The optimum solution is then obtained by using traditional gradient-based search algorithm functionality “fmincon” in commercial Matlab package.