Material extrusion‐based additive manufacturing, also known as fused filament fabrication (FFF) or 3D printing facilitates the fabrication of cranial implants with different materials and complex internal structures. The impact behavior plays a key role in the designing process of cranial implants. Therefore, the performance of impact tests on novel implant materials is of utmost importance. This research focuses on investigating the dependency of the infill density and pattern on the impact properties of 3D‐printed poly(methyl methacrylate) (PMMA) sandwich specimens including internal rectilinear, gyroid, and 3D‐honeycomb (3D‐HC) structures. 3D‐HC structures show higher impact forces and dissipated energies as well as dynamic stiffness values compared to rectilinear and gyroid structures at the same infill density. 70% infill 3D‐HC and 100% infill rectilinear structures prove to be most promising. In addition, two different optimization techniques to further improve the impact properties of these specimens, namely a material and a topology optimization, are applied. Topology optimization shows promising results until first damage and material optimization regarding dissipated energies. However, both are not able to outperform the 3D‐HC pattern.