Promoted Cu/ZnO catalyst was synthesized on Al2O3-ZrO2 support. Effects of calcination conditions on the catalytic performance in a CO2 hydrogenation reaction were studied systematically using the response surface methodology (RSM). The application of RSM with rotatable central composite design (RCCD) for optimization on the influence of catalyst’s calcination variables on the CO2 conversion and methanol selectivity is presented. The calcination variables studied include temperature, A (181–518 °C), ramping rate, B (1–30 °C/min), and duration, C (1–7 h). From the RSM-generated model, the optimum calcination condition for this catalyst was 350 °C with 17.5 °C/min ramping rate for a 4 h duration. At the optimum calcination condition, the catalyst exhibited a Brunauer–Emmett–Teller (BET) surface area of 147 m2/g, a pore volume of 0.31 cm3/g, and a pore diameter of 8.1 nm.