h i g h l i g h t s• Investigation of TSS, H 2 O 2 dosage, pH and interactions on MW sludge pretreatment.• Quadratic models were drawn for 16 response variables with good predictive ability.• Models could optimize the treatment process for multiple disintegration objectives. a r t i c l e i n f o ) has been shown to offer considerable advantages owing to its flexible control, low overall cost, and resulting higher soluble chemical oxygen demand (SCOD); accordingly, the method has been proposed recently as a means of improving sludge disintegration. However, the key factor controlling this sludge pretreatment process, pH, has received insufficient attention to date. To address this, the response surface approach (central composite design) was applied to evaluate the effects of total suspended solids (TSS, 2-20 g/L), pH (4-10), and H 2 O 2 dosage (0-2 w/w) and their interactions on 16 response variables (e.g., SCOD released , pH, H 2 O 2 remaining ). The results demonstrated that all three factors affect sludge disintegration significantly, and no pronounced interactions between response variables were observed during disintegration, except for three variables (TCOD, TSS remaining , and H 2 O 2 remaining ). Quadratic predictive models were constructed for all 16 response variables (R 2 : 0.871-0.991). Taking soluble chemical oxygen demand (SCOD) as an example, the model and coefficients derived above were able to predict the performance of microwave pretreatment (enhanced by H 2 O 2 and pH adjustment) from previously published studies. The predictive models developed were able to optimize the treatment process for multiple disintegration objectives.