This paper presents a numerical study of a blast-resistant design of reinforced concrete panels with a novel auxetic reinforcement layout inspired by auxetic materials, which have a negative Poisson’s ratio, i.e., shrink under compression and expand under tension. A series of two-way supported panels reinforced with re-entrant auxetic-shaped rebars were numerically tested under a TNT explosion. The high-fidelity multi-physics explicit solver of LS-DYNA was utilized to analyze the efficiency of the proposed design. Firstly, the incident pressure of a TNT explosion data and the structural response of a conventional reinforced concrete panel under a TNT explosion were successfully validated by comparing with the experimental and empirical results. Secondly, the blast-resistant capacity of the proposed model was evaluated in comparison to two different conventional designs. Moreover, a parametric study was carried out to reveal the driving parameters of the newly proposed auxetic-shaped reinforcement design. It has been proved that the proposed auxetic reinforcement layout significantly reduces the spalling radius and increases the energy absorption capacity of panels. As a result of the parametric study, the increased reinforcement volume ratio was ineffective on the spalling radius, although the cell size of auxetic reinforcement was found to be quite effective for the blast-resistant design of concrete panels. Overall, the proposed re-entrant auxetic reinforced panel performed far better than conventional designs under blast load. With the recent developments in 3D printing technology, the proposed auxetic reinforcement layout is a strong candidate to deal with blast-resistant designs of concrete panels.