Abstract: A multilayer approach to the midcourse trajectory design and terminal phase time constants design for a surface-to-air missile to maximize the kill probability was presented. Three layers were discussed. The first layer represented the midcourse trajectory of the missile, the second layer represented the terminal homing phase, and the third layer was the warhead damaging process. A layer can be seen as a subsystem, the multilayer trajectory optimization problem is a essential multidisciplinary design optimization (MDO) problem. The global sensitivity equation (GSE) method was adopted to compute sensitivity derivatives with respect to design variables, which did optimization in system level and got the trajectory which maximizing the kill probability. At last a case of intercepting air-to-surface missile(ASM) was designed and optimized. Uniform design of experiments and BP neural network were used to avoid long time computing. The result is that GSE method is effetive for multilayer trajectory optimization design problem.