An explosive attack on a vehicle can cause catastrophic damage, injury, and loss of life. Experimentally evaluating the blast performance is very costly, hazardous, and environmentally polluting. The numerical investigation of blast behavior is a good alternative. However, this numerical study showed an effort toward improving metallic sandwich panels’ ability to withstand explosion loads of 1–3 kg of TNT at a distance of 100 mm. The blast mitigation of square and circular tube honeycomb cores was compared. The foam and circular tube stiffeners were used to optimize the honeycomb sandwiches’ blast mitigation characteristics. Radial face deflection, face center deflection, core crushing behavior, internal energy, and plastic dissipation energy parameters were used for the characterization of blast behavior. The obtained results indicate that the circular tube honeycomb has better blast mitigation characteristics than the square honeycomb, which improves with foam filling. The circular tube-strengthened square honeycomb provides the lightest stiffened sandwich panel with the smallest deformation and face deflections under all explosive loadings.