This work investigates the impact of catalyst structuring into particles or monoliths on methanol production from only CO2 and H2 at a large scale. Methanol synthesis in multi-tubular reactors is evaluated using packed-bed and monolithic reactors by modeling heat and mass transfer in each reactor. The obtained simulation results show that, at low gas hourly space velocity (GHSV = 10,000 h−1), the performances of both reactor technologies are similar. In this case, the packed-bed reactor technology is the most appropriate technology due to its simplicity of installation and operation. At high GHSV (25,000 h−1), the packed-bed reactor technology is limited by a considerable pressure drop that causes an important loss in productivity due to thermodynamic equilibrium, whereas the monolithic reactors exhibit negligible pressure drop and achieve far better performances.