In this work, a strategy for hybrid treatment was proposed, aiming to present a hybrid impregnation agent including lignin-derived resin (LR) and surface-modified montmorillonite (GMMT) to treat fast-growing poplar wood. The treating agents could penetrate the wood, fill the cavities of the wood interior, and strengthen the cell wall structure. The optimal WPG of 36.2% was obtained upon the response surface methodology (RSM) at the conditions of 34% LR, 1.8% GMMT, 1.2 MPa impregnation pressure, and 99 min impregnation time. The density, water uptake (WU), modulus of rupture (MOR), modulus of elasticity (MOE), and compressive strength (CS) of the samples were tested to evaluate the enhancement of the physical and mechanical properties. In addition, these samples were investigated via cone calorimeter (CONE), Fourier Transform Infrared spectrometer (FTIR), and X-ray diffraction (XRD). The results showed that the density of the treated samples increased significantly up to 0.72 g/cm³. Compared with 134.8% of the control, the WU of the treated wood sample could decrease to 60.3%. In addition, the MOR and MOE of the resulting samples reached up to 131.8 MPa and 18.14 GPa, respectively, which were 62.3% and 77.7% higher than the control. Notably, the CS was 84.7 MPa with an increase of up to 94.7%. Moreover, the peak heat release rate (HRR) of the treated sample was obviously reduced to 231.33 kW/m², a decrease of 17.5% compared to the control (271.71 kW/m²).