This study explores the effect of high-solids loading for a fed batch enzymatic hydrolysis and fermentation. The solids loading considered was 19%, 30% and 45% using wheat straw and corn stover as a feedstock. Based on the experimental results, techno-economic analysis and life cycle assessments were performed. The experimental results showed that 205 ± 25.8 g/L glucose could be obtained from corn stover at 45% solids loading after 96 h which when fermented yielded 115.9 ± 6.37 g/L ethanol after 60 h of fermentation. Techno-economic analysis showed that corn stover at 45% loading yielded the highest ROI at 8% with a payback period less than 12 years. Similarly, the global warming potential was lowest for corn stover at 45% loading at −37.8 gCO2 eq./MJ ethanol produced.