To optimize the Sabatier process, quaternary supported catalyst materials are synthesized and tested. The syntheses are performed by the industrially established, reproducible and automated methods of impregnation and sol–gel synthesis. The screening of the 588 quaternary catalysts is carried out in a specially designed 10-fold parallel gas flow micro-structured reactor as wall catalysts in sequential operation mode at a temperature of T = 573 K and a pressure of p = 15 bar. For the description of the activity, the reaction parameters CO2 conversion, CH4 yield, and CH4/CO2 selectivity are used. These are determined by analyses of the gas phase composition using µGC-FID. The catalysts with the highest activities are validated in a micro-structured reactor with similar characteristics as the screening reactor in the temperature range between T = 573–673 K and a pressure of p = 15 bar. Characterization by powder X-ray diffraction, Raman spectra, and scanning transmission electron microscopic images data on the phase and element distribution after calcination and reduction was conducted.