Commercial scale cellulosic biorefineries face significant challenges to produce low-cost fermentable sugar from biomass. Biorefinery processing steps are interrelated and trade-offs between process parameters impact the cost and efficiency of the overall system. Although densified biomass as a biorefinery feedstock would improve biomass supply logistics, it has not been considered viable due to high energy and emissions associated with the densification process. However, the potential synergies of biomass densification with downstream processing steps are critical. An energy-efficient system with improved supply logistics, reduced severity pretreatment, and improved hydrolysis efficiency will lower the cost of sugar production from cellulosic biomass. The objective of this research was to increase overall process efficiency of biorefineries by understanding how different process parameters affect the hydrolysis efficiency. Processing trade-offs in pretreatment and enzymatic hydrolysis for densified and non-densified biomass for economical sugar production were evaluated. A life cycle perspective was taken to compare fossil energy and greenhouse gas (GHG) emissions from pelleted and non-pelleted corn stover during transportation and soaking in aqueous ammonia (SAA) pretreatment. A model developed to demonstrate the interaction of enzymatic hydrolysis factors to improve hydrolysis efficiency showed that enzyme loadings had a more significant effect on hydrolysis rates than pH or temperature. Economical optimal enzyme loadings were lower than loadings to maximize yield, loadings can be adjusted to maximize profit based on enzyme costs, ethanol price, and process temperature. Pelleted corn stover allowed reduction in SAA-pretreatment severity with different combinations of temperature, time, and ammonia concentration to produce 90% or higher glucose yields. This suggests possible economic and environmental benefits of using pelleted biomass as a biorefinery feedstock. Use of pelleted biomass reduced transportation fossil energy and GHG emissions by 25%. A significant reduction of energy (89%) for SAA-pretreatment was achieved with pelleted biomass due to lower pretreatment time and higher solid loadings. Use of pelleted biomass allowed doubling of pretreatment solid loadings, which lowered pretreatment reactors from 59 to 9, in addition to associated water and chemical savings. This study demonstrated that SAA pretreatment is not feasible for non-pelleted biomass, but process synergies make SAA pretreatment possible for pelleted biomass.