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 6 min at 300 W yielded solid fractions that on hydrolysis resulted in maximum reducing sugar yield of 0.495 g/g. The energy required for AAMP at 300 W for 6 min was 108 kJ whereas high pressure pretreatment (180°C, 100 rpm for 45 min) requires 5 times more energy i.e., 540 kJ. Physiochemical characterization of native and pretreated feedstock revealed differences between high pressure pretreatment and AAMP.