Lattice truss core sandwich composite (LTCSC) panels can exhibit high compressive performance until failure is caused by compressive fracture of the composite strut. Early failure of the core-facesheet and central nodes, as well as fiber misalignment, can hinder the full potential of an LTCSC. This study aimed at improving the compressive stiffness and strength of LTCSC panels through minimizing the fiber misalignment and fabrication issues, while strengthening the central and core-facesheet nodes. The lost-molding technique was used to fabricate LTCSC panels, which were then subjected to quasi-static flatwise compression testing. Relative positioning of neighboring composite struts, modification of the carbon fiber path, and strengthening of the core-facesheet node significantly improved the compressive performance of the panels. Based on the findings, compressive strength and stiffness of LTCSC panels can be improved about 100% and 300%, respectively, with minimal increase in weight. Fabricated LTCSC panels were found to demonstrate competitive specific compressive properties in comparison with conventional core materials.