Even though the characteristics of polymer materials are sensitive to temperature, the mechanical properties of polymer nanocomposites have rarely been studied before, especially for the fatigue behavior of hybrid polymer nanocomposites. Hence, the tensile quasi-static and fatigue tests for the epoxy nanocomposites reinforced with multi-walled carbon nanotubes (CNTs) and graphene nanoplatelets (GNPs) were performed at different temperatures in the study to investigate the temperature-dependent synergistic effect of hybrid nano-fillers on the studied properties. The temperature and the filler ratio were the main variables considered in the experimental program. A synergistic index was employed to quantify and evaluate the synergistic effect of hybrid fillers on the studied properties. Experimental results show that both the monotonic and fatigue strength decrease with increasing temperature significantly. The nanocomposites with a MWCNT (multi-walled CNT): GNP ratio of 9:1 display higher monotonic modulus/strength and fatigue strength than those with other filler ratios. The tensile strengths of the nanocomposite specimens with a MWCNT:GNP ratio of 9:1 are 10.0, 5.5, 12.9, 23.4, and 58.9% higher than those of neat epoxy at −28, 2, 22, 52, and 82 °C, respectively. The endurance limits of the nanocomposites with this specific filler ratio are increased by 7.7, 26.7, 5.6, 30.6, and 42.4% from those of pristine epoxy under the identical temperature conditions, respectively. Furthermore, the synergistic effect for this optimal nanocomposite increases with temperature. The CNTs bridge the adjacent GNPs to constitute the 3-D network of nano-filler and prevent the agglomeration of GNPs, further improve the studied strength. Observing the fracture surfaces reveals that crack deflect effect and the bridging effect of nano-fillers are the main reinforcement mechanisms to improve the studied properties. The pullout of nano-fillers from polymer matrix at high temperatures reduces the monotonic and fatigue strengths. However, high temperature is beneficial to the synergistic effect of hybrid fillers because the nano-fillers dispersed in the softened matrix are easy to align toward the directions favorable to load transfer.