Abstract: The plywood made from pMDI resin that does not release formaldehyde has important applications in the construction and furniture fields. However, faces disadvantages such as high cost, high penetration, and low fire-retardant performance during use. Here, we introduce an innovative nano-modified resin method, which uses nanomaterials as fillers to prepare nano-modified pMDI resin. The resulting plywood exhibits higher mechanical strength and fire resistance. Three types of nanomaterials with different dimensions were selected to evaluate their modification effects. The key to this modification effect is to fill the adhesive layer with nanomaterials that have high compatibility with pMDI and allow them to react with isocyanate to form a cross-linked network structure. The results show that compared with the original pMDI, the plywood prepared with the modified resin has higher bonding strength (increased by 62.6%) and less residual isocyanate. Moreover, the nanomaterials can significantly increase the curing rate of the resin, the stress transfer efficiency, and the adhesive layer strength. Meanwhile, the limited oxygen index test indicates that the addition of HNTs and nano-SiO₂ has an enhancing effect on the fire-retardant performance. The above research results confirm the effectiveness of nanomaterials in improving the fire-retardant performance of wood-based panels and provide a technical path for manufacturing fire-retardant wood-based panels with balanced mechanical properties.