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Anaerobic digestion is a popular sewage sludge (Ss) treatment method as it provides significant pollution control and energy recovery. However, the low C/N ratio and poor biodegradability of Ss necessitate pretreatment methods that improve solubilization under anaerobic conditions in addition to anaerobic co-digestion with other substrates to improve the process efficiency. In this study, three pretreatment methods, namely microwave irradiation, ultrasonication, and heat treatment, were investigated, and the corresponding improvement in methane production was assessed. Additionally, the simplex centroid design method was utilized to determine the optimum mixture ratio of food waste (Fw), livestock manure (Lm), and Ss for maximum methane yield. Microwave irradiation at 700 W for 6 min yielded the highest biodegradability (62.0%), solubilization efficiency (59.7%), and methane production (329 mL/g VS). The optimum mixture ratio following pretreatment was 61.3% pretreated Ss, 28.6% Fw, and 10.1% Lm. The optimum mixture ratio without pretreatment was 33.6% un-pretreated Ss, 46.0% Fw, and 20.4% Lm. These results indicate that the choice of pretreatment method plays an important role in efficient anaerobic digestion and can be applied in operational plants to enhance methane production. Co-digestion of Ss with Fw and Lm was also beneficial. KCI Citation Count: 5