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This paper examines the impact of polyurethane foam (PUF) filling on the dynamic response of honeycomb sandwich beams (HSBs) through the blast testing. The HSBs are composed of steel face sheets and an aluminium alloy honeycomb core filled with PUF. A comparative analysis of damage modes is conducted between conventional hexagonal and auxetic HSBs, considering both foam-filled and unfilled configurations. The results reveal that the HSBs with foam filling demonstrate significantly enhanced blast performance compared to their counterparts without foam filling. This superiority is evident in both global deformation and local damage characteristics. Furthermore, a well-validated numerical model is developed to examine the damage mechanisms of PUF-filled HSBs under blast loading. The investigation reveals that appropriate PUF filling methods can effectively enhance bending resistance while minimizing the decline in the energy absorption efficiency. Finally, a multiobjective optimization was conducted using the back-propagation (BP) neural network and the SPEA2 algorithm to identify the optimal position for PUF. By utilizing a reduced foam filling approach as opposed to completely filling the structure, the two optimized configurations show a decrease in deformation of 5.38 % with an equivalent specific energy absorption (SEA) or an increase in the SEA by 5.26 % with an equivalent deformation. [ABSTRACT FROM AUTHOR]