Polymers have an excellent effect in terms of moderating fast neutrons with rich hydrogen and carbon, which plays an indispensable role in shielding devices. As the shielding of neutrons is typically accompanied by the generation of γ-rays, shielding materials are developed from monomers to multi-component composites, multi-layer structures, and even complex structures. In this paper, based on the typical multilayer structure, the integrated design of the shield component structure and the preparation and performance evaluation of the materials is carried out based on the design sample of the heat-resistant lightweight polymer-based interlayer. Through calculation, the component structure of the polymer-based materials and the three-layer thickness of the shield are obtained. The mass fraction of boron carbide accounts for 11% of the polymer-based material. Since the polymer-based material is the weak link of heat resistance of the multilayer shield, in terms of material selection and modification, the B4C/TiO2/polyimide molded plate was prepared by the hot-pressing method, and characterization analysis was conducted for its structure and properties. The results show that the ball milling method can mix the materials well and realize the uniform dispersion of B4C and TiO2 in the polyimide matrices. Boron carbide particles are evenly distributed in the material. Except for Ti, the other elemental content of the selected areas for mapping is in good agreement with the theoretical values of the elemental content of the system. The prepared B4C/TiO2/polyimide molded plate presents excellent thermal properties, and its glass transition temperature and initial thermal decomposition temperature are as high as 363.6 °C and 572.8 °C, respectively. In addition, the molded plate has good toughness performs well in compression resistance, shock resistance, and thermal aging resistance, which allows it to be used for a long time under 300 °C. Finally, the prepared materials are tested experimentally on an americium beryllium neutron source. The experimental results match the simulation results well.