In the present work, alkali assisted microwave pretreatment (AAMP) of cotton plant residue (CPR) with high pressure reactor pretreatment was compared. Further, modeling of AAMP was attempted. AAMP, followed by enzymatic saccharification was evaluated and the critical parameters were identified to be exposure time, particle size and enzyme loading. The levels of these parameters were optimized using response surface methodology (RSM) to enhance sugar yield. AAMP of CPR (1mm average size) for 6min at 300W yielded solid fractions that on hydrolysis resulted in maximum reducing sugar yield of 0.495g/g. The energy required for AAMP at 300W for 6min was 108kJ whereas high pressure pretreatment (180°C, 100rpm for 45min) requires 5 times more energy i.e., 540kJ. Physiochemical characterization of native and pretreated feedstock revealed differences between high pressure pretreatment and AAMP.