This study assessed the effect of slicer-made interlocking joints on 3D printed sandwich panels manufactured through fused filament fabrication (FFF) in terms of flexural properties and energy absorption. Composites were prepared with thermoplastic polyurethane (TPU) as the core material and polyamide (PA), polylactic acid (PLA), polyethylene terephthalate (PET) as skin materials for each of the three composites, respectively. In order to assess the implications of internal geometry, 3D printing was done on five infill topologies (Cross-3D, Grid, Gyroid, Line and Honeycomb) at 20% density. All samples had 20% core density and underwent three point bending testing for flexural testing. It was noted that the Grid and Gyroid cores had the best performance in terms of maximum load capacity based on stretch-dominated behavior while Cross-3D and Honeycomb had lower strengths but stable moments during the bending process. Since Cross-3D topology offered the lowest deflection, it was selected for further experiments with slicer added interlocks at the face–core interface. This study revealed the most notable improvements as gains of up to 15% in peak load, 48% in maximum deflection, and 51% in energy absorption compared with the non-interlocked designs. The PET/TPU interlocked demonstrated the best performance in terms of the energy absorption (2.45 J/mm³) and peak load (272.6 N). In contrast, the PA/TPU interlocked exhibited the best flexibility and ductility with a mid-span deformation of 21.34 mm. These results confirm that slicer-generated interlocking interfaces lead to better load capacity and energy dissipation, providing a lightweight, damage-tolerant design approach for additively manufactured sandwich beams.