Response surface methodology (RSM) with central composite design (CCD) was applied to determine the composition of an alumina-supported nickel-iron (Ni-Fe) catalyst that provided the highest CH4 yield for the CO2 hydrogenation reaction. This involved synthesis of alumina-supported Ni-Fe catalysts of compositions that were specified by CCD. The catalysts were then tested for the CO2 hydrogenation reaction, and a model equation was developed that related the catalyst composition to the CH4 yield. The model equation was validated by analysis of variance, and it was found to adequately represent the experimental data. The model equation predicted that the alumina-supported Ni-Fe catalyst containing 32.8% Ni and 7.7% Fe would provide the highest CH4 yield. A catalyst with this specific composition and the same metal deposition method and two other catalysts of the same composition but different metal deposition metal were also synthesized, characterized, and tested for the CO2 hydrogenation reaction. The three catalysts did show activities similar to those predicted by the model equation. Furthermore, characterization and reaction studies revealed that the three catalysts were similar, suggesting that the metal deposition methods do not have any effect on the catalytic activity.