The present chapter deals with optimum design of structures for earthquake induced loads by taking into account nonlinear time history structural response. As the structural seismic optimization is a time consuming and computationally intensive task, in this chapter, a methodology is proposed to reduce the computational burden. The proposed methodology consists of an efficient optimization algorithm and a hybrid neural network system to effectively predict the nonlinear time history responses of structures. The employed optimization algorithm is a modified cellular genetic algorithm which reduces the required generation numbers compared with the standard genetic algorithm. Also, the hybrid neural network system is a combination of probabilistic and generalized regression neural networks. Numerical results demonstrate the computational merits of the proposed methodology for seismic design optimization of structures.