As an indispensable pre-treatment for aging, homogenization treatment has a significant effect on precipitation behavior of the Mg-RE alloys. Herein, the influence of homogenization temperature on the microstructure evolution and mechanical performance of a novel Mg-2.0Nd-2.0Sm-0.4Zn-0.4Zr (wt.%) alloy has been studied systematically. The results indicated that the as-cast alloy was mainly composed of α-Mg matrix, β-Mg12(Nd,Sm,Zn) phase and Zr-containing particles. Upon increasing the homogenization temperature from 500 oC to 525 oC for 8 h, the average grain size of as-homogenized alloy increased from 76 μm to 156 μm, and the content of β phase decreased gradually. It was worth noting that the homogenization temperature exceeded 515 oC, the β phase at the grain boundaries was completely dissolved. After aging at 200 oC for 18 h, numerous of plate-like β' phases were observed in α-Mg matrix. The rise in homogenization temperature was conducive to nucleation and growth of the β' phase. However, excessive homogenization temperature significantly coarsened grain size. The aged alloy under homogenization treatment at 515 oC for 8 h achieved optimal mechanical properties. The values of ultimate tensile strength, yield strength and elongation were 261 MPa, 154 MPa and 5.8 %, respectively. The fracture mode of the aged alloy mainly exhibited a typical transgranular cleavage fracture.