To improve the performance of a soy flour (SF)-based adhesive, a low-cost hydroxymethyl melamine prepolymer (HMP) was synthesized and then used to modify the SF-based adhesive. The HMP was characterized, and the performance of the adhesive was evaluated, including its residual rate, functions, thermal stability, and fracture section. Plywood was fabricated to measure wet shear strength. The results indicated that the HMP preferentially reacted with polysaccharose in SF and formed a cross-linking network to improve the water resistance of the adhesive. This polysaccharose-based network also combined with the HMP self-polycondensation network and soy protein to form an interpenetrating network, which further improved the water resistance of the adhesive. With the addition of 9% HMP, the wet shear strength (63 °C) of the plywood was 1.21 MPa, which was 9.3 times that of the SF adhesive. With the HMP additive increased to 15%, the shear strength (100 °C) of the plywood was 0.79 MPa, which met the plywood requirement for exterior use (≥0.7 MPa) in accordance with Chinese National Standard (GB/T 9846.3-2004). With the addition of 9% and 15% HMP, the residual rates of the adhesive improved by 5.1% and 8.5%, respectively. The dense interpenetrating network structure improved the thermal stability of the resultant adhesive and created a compact fracture to prevent moisture intrusion, which further increased the water resistance of the adhesive.