Optimizing anaerobic digestion aims to maximize organic waste stabilization at shortdigestion period with higher biogas production. This paper presents different strategies tooptimize the anaerobic digestion of organic fraction of municipal solid waste in combinedprocess in which early flushing and microaeration were conducted during pre-stage, Also, theinfluence of substrate particle size reduction and the advantage of thermophilic system overmesophilic in the overall digestion process are presented, Additionally, an attempt was takento employ sequential staging concept by using a mature (old) reactor which underwent acombined digestion process. Importantly, process evaluation between an optimized combinedprocess and sequential staging concept were evaluated with the main objective of optimizingthe process, Process efficiency evaluation was based on biochemical methane potential(BMP) test The overall result suggest that the combined anaerobic digestion process can beoptimized by conducting shorter duration of pre-stage at reduced volume of flushing waterwith microearation, under thennophilic condition at reduced substrate particle size of 30 mm,Nevertheless, the sequential staging concept offers an improved operation over the combinedanaerobic digestion wherein the higher specific methane yield of 11.9 L CH4/kg VS.day wasachieved, Improved waste stabilization with 86% and 79% mass and volume reduction whichcorresponds to 84% process efficiency was obtained by sequential staging process,