To determine optimized conditions for co-digestion for a mixture of four kinds of mixed vegetable crop residues consisting of cucumber, tomato, eggplant, and pepper mixed in equal parts on a mass basis, codigestion experiments were carried out with pig manure. The interaction effects of parameters such as manure-to-mixed vegetable residues ratios (M/S), initial pH, and organic load (OL) were investigated with respect to cumulative methane yield using response surface methodology (RSM). The highest cumulative methane yield was calculated to be 380.50 mL/g VS at an initial pH of 7.3, OL of 18.8 g VS/L, and M/S of 3.9:1. Comparison and veri cation experiments showed that under optimized conditions the co-digestion process showed increased the methane yield and had practical application value. The microbial analysis showed that the relative abundances of bacterial taxa, such as Clostridium_sensu_stricto_1, Fastidiosipila, and Terrisporobacter, were all highest in the co-digestion samples under optimized process conditions (PV). Different types of methanogenic archaea taxa in PV samples were richer than other samples, which showed higher relative abundances of Methanogenium, Methanobrevibacter, Methanoplanus, Methanospirillum, and Methanobrevibacter. Thus, the co-digestion system of a mixture of vegetable residues and pig manure can enrich different types of methanogenic archaea taxa, which leads to increased digestion performance, and may strengthen process stability. Importantly, pig manure, mixed vegetable residues can be included into anaerobic digestion applications through co-digestion, thus enabling valorization of these substantial residues and can be engineered for applications.