Large scale production sites for the generation of the basic chemical methanol are capital and energy intensive. The design of a synthesis loop configuration is crucial to the conceptual design phase and finally decisive for the overall plant performance and the economics. Industrial synthesis loop configurations are complex systems and have to be highly efficient, in order to meet the requirements in terms of cost efficiency and environmental impact. The two major technologies used in the industry refer to direct cooled quench reactor systems and indirect cooled isothermal reactor systems. The utilization of carbon dioxide in chemical synthesis for further valorization to more valuable products is a topic which gained large attention in the recent years. The integration of CO2 into the synthesis of the bulk chemical methanol not only can have a remarkable ecological contribution but also reduce the required feedstock (typically fossil fuels) and consequently also the production costs. This study focusses on the economic design optimization of commercial synthesis loop configuration with integration of CO2 as a feedstock. The optimal design conditions and minimum methanol costs are determined using the sequential quadratic programming (SQP) technique. Design aspects such as the CO2 inlet concentration for injection, the catalyst bed dimensions, the quench ratio, the split ratio as well as operation parameters including the temperature and pressure are the variables determined by the optimization algorithm. The results show that the minimum levelized product cost for methanol are highly dependent on the CO2 inlet fraction. The minimum methanol price is in the range of 500 – 2000 US$. The constructional design of the components as well as the process parameters show a large sensitivity to changes in the boundary conditions.