Multi-objective optimization of aerodynamic layout is a key technology in aircraft design. A new multi-objective optimization method is proposed for aerodynamic shape parameters of hypersonic reentry vehicle, and then the influence of the method on the performance of hypersonic reentry vehicle is proved. Through example simulation, the influence of drag and lift on guidance performance is verified and analyzed in detail, with 3 performance indicators, including circular error probable of aircraft landing point, proportion of landing speed greater than 500 m/s, and proportion of maximum flight overload less than 60g, set as the optimization objective. By taking lift characteristics as intermediate parameters, the aerodynamic layout optimization problem divided into two sub problems. Through the lift characteristic optimization based on search algorithm and the shape parameter optimization based on an improved simulated annealing algorithm, the optimization calculation time is reduced, the calculation efficiency is improved, thus optimizing the overall aerodynamic layout of the main body and flap of the aircraft, and obtaining the best aircraft shape under hypersonic flow. The simulation results show that under determined constraints, the optimization algorithm increases the aerodynamic lift of the aircraft under supersonic flow and effectively improves the lift drag ratio. On the premise of not affecting the maximum flight overload, the optimized aircraft shows higher aerodynamic performance, and significantly improved hit accuracy, with the landing speed in compliance with the index requirements, and the performance of the guidance system effectively improved.