Based on the mechanical characteristics of the core layer, which withstands the shear stress and deformation of a sandwich beam, a topology optimization framework based on the bi-directional evolutionary structural optimization method is proposed to optimize the core layer composed of a periodic base cell with extreme shear stiffness. The effects of the volume fraction, filter radius, and initial periodic base cell (PBC) aspect ratio on the micro-topology of the core and the dynamic response process, core compression, and energy absorption capacity of the sandwich beams under blast impact loading were analyzed by the finite element method. The results demonstrated that the over-pressure action stage was coupled with the core compression stage. Under the same loading and mass per unit area, the sandwich beam with a 20% volume fraction core layer had the best blast resistance. The filter radius has a slight effect on the shear stiffness and blast resistances of the sandwich beams, but increasing the filter radius could slightly improve the bending stiffness. Upon changing the initial PBC aspect ratio, there are three methods for PBC evolution: the first is to change the angle between the adjacent bars, the second is to further form holes in the bars, and the third is to combine the first two methods. However, not all three methods can improve the energy absorption capacity of the structure. Changing the aspect ratio of the PBC arbitrarily may lead to worse results. More detailed studies are necessary if further optimization is to be achieved.