Background This study investigated the feasibility of enhancing anaerobic digestion of sewage sludge with triple, dual, and individual pre-treatment of waste activated sludge with heat, alkalinity, and hydrogen peroxide. These pre-treatments disrupt sludge flocs, organisms’ cell walls, extracellular polymeric substance, and intracellular organic matter, which increase biodegradability and hydrolysis rate of organic matter. In addition, the influence of various variables on methane production was analyzed using the response surface methodology with the quadratic model. Eventually, an optimized temperature and chemical concentration for the highest methane production and lowest chemical usage is suggested.Results The highest amount of methane production was obtained from the sludge pretreated with triple pretreatment (heat (90°C), alkalinity (pH=12), and hydrogen peroxide (30 mg H2O2 /g TS)), which had better performance with 96% higher than that of the control sample with Temperature of 25°C approximately and alkalinity of pH=8. Response surface methodology with the quadratic model was also used for analyzing the influence of temperature, pH, and hydrogen peroxide concentration on anaerobic digestion efficiency. It was revealed that the optimized temperature, pH, and hydrogen peroxide concentration for maximizing methane production and solubilisation of organic matter and minimizing thermal energy and chemical additives of the pre-treatments are 83.2°C, pH=10.6 and 34.8 mg H2O2 /g TS, respectively, has the desirability of 0.67.Conclusion This study reveals that triple pre-treatment of waste activated sludge performs better than dual and individual pre-treatment, Respectively. The enhanced methane production can be used as an important renewable energy resource in wastewater treatment plants for producing electrical and thermal energy. Furthermore, exploiting a higher amount of methane in the anaerobic digestion stage decreases methane emission to the atmosphere in dewatering and landfilling stages and enhances the quality of digested sludge, bringing about environmentally friendly and economically attractive sewage sludge treatment process.