Design optimization of structural systems is often iterative, time consuming and is limited by the knowledge of the designer. For that reason, a rapid design optimization scheme is desirable to avoid such problems. This paper presents and integrates two design methodologies for efficient conceptual design of structural systems involving computationally intensive analysis. The first design methodology used in this paper is structural modification technique (SMT). The SMT utilizes the frequency response functions (FRFs) of the original model for the reanalysis of the structure that is subjected to structural modification. The receptances of the original structure are coupled with the dynamic stiffness of the components that are added to or removed from the original structure to perform the structural modification. Then, the coupled matrices are used to calculate the mobility matrices of the modified structure in an efficient way. The second design methodology used in this paper is neural networks (NN). Once sufficient input and output relationships are obtained through SMT, a NN model is constructed to predict the FRF curves of the system for further analysis of the system performance while experimenting different design parameters. The input–output sets used for training the network are increased by applying an interpolation scheme to improve the accuracy of the NN model. The performance of the proposed method integrated through SMT and NN technique is demonstrated on a rectangular plate to observe the effect of the location and thickness of stiffeners on the frequency response of the structure. It is observed that both methods combined with the proposed interpolation scheme work very efficiently to predict the dynamic response of the structure when modifications are required to improve the system performance.