Methanol production via carbon dioxide (CO2) hydrogenation is a green chemical process, which can reduce CO2 emission. The operating conditions for minimum methanol production cost of three configurations were investigated in this work. An artificial neural network with Latin hypercube sampling technique was applied to construct model-represented methanol production. Price sensitivity was performed to study the impacts of the raw materials price on methanol production cost. Price sensitivity results showed that the hydrogen price has a large impact on the methanol production cost. In mathematical modeling using feedforward artificial neural networks, four different numbers of nodes were used to train artificial neural networks. The artificial neural network with eight numbers of nodes showed the most suitable configuration, which yielded the lowest percent error between the actual and predicted methanol production cost. The optimization results showed that the recommended process design among the three studied configurations was the process of methanol production with two reactors in series. The minimum methanol production cost obtained from this configuration was $888.85 per ton produced methanol, which was the lowest methanol production cost among all configurations.