Anaerobic digestion (AD) of sewage sludge is associated with lowered carbon conversion efficiency due to the recalcitrance of microbial cells in the Waste Activated Sludge (WAS) from the aeration basins with 50 % of the dry weight still being present after AD. The effect of Advanced Wet Oxidation & Steam Explosion (AWOEx) pretreatment on the methane yield at variable temperatures (165–200 °C), residence time (15–45 min) and oxygen dosage (1%–10% based on VS concentration) was tested in this study. Central composite design (JMP® Pro) was used to design 19 runs of AWOEx pretreatment of dewatered digested sewage sludge (DADSS) at different operating conditions. After pretreatment the DADSS was fed to 19 bioreactors operated in semi-continues mode at 37 °C. The highest average methane yields of 183 mL/g VS and 170 mL/g VS were found for the bioreactors receiving DADSS pretreated at 165 °C with a retention time of 15 min and 10 % O 2 (Condition 1), and, 182.5 °C with a retention time of 15 min and 5.5 % O 2 (Condition 2). This corresponds to an increase in the methane production of 156.2 % and 140.5 % compared to the methane production from the DADSS without pretreatment. Plotting the results using the response surface model showed that temperature and O 2 dosage had a significant effect on the methane yield while residence time was of lower importance. Importantly, thermic treatment without oxygen showed far lower methane yields of 114.5 mL/gVS and 120.26 mL/gVS, respectively of the two best conditions described above. Through this two-step AD process, we were able to achieve a net 94% improved methane yield compared to conventional AD of sewage sludge by implementing a second AWOEx pretreatment step (followed by secondary AD) with 26.9% decreased organics content, further reducing the cost of the final disposal of the treated sewage sludge. • AWOEx pretreated sludge tested for CH 4 yield at variable temperature, residence time and O 2 dosage. • JMP Pro was used to design 19 differential runs of AWOEx pretreated DADSS. • Pretreated DADSS was fed to 19 bioreactors operated in semi-continues mode at 37 °C. • Optimal average CH 4 yield of 183 mL/g VS was obtained for 165 °C, 15 min and 10% O 2 . • 94% improved methane yield compared to conventional AD of sewage sludge.