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•Biomass composition, structural variability are key players in lignocellulosic biorefinery.•Cellulosic ethanol production has immense potential to be use as transportation fuels.•Efficient pretreatment and achieving high sugar/ ethanol titer are critical challenge.•State-of-the-art technology development, genetic engineering key area for exploration.
Cellulosic ethanol production has received global attention to use as transportation fuels with gasoline blending virtue of carbon benefits and decarbonization. However, due to changing feedstock composition, natural resistance, and a lack of cost-effective pretreatment and downstream processing, contemporary cellulosic ethanol biorefineries are facing major sustainability issues. As a result, we've outlined the global status of present cellulosic ethanol facilities, as well as main roadblocks and technical challenges for sustainable and commercial cellulosic ethanol production. Additionally, the article highlights the technical and non-technical barriers, various R&D advancements in biomass pretreatment, enzymatic hydrolysis, fermentation strategies that have been deliberated for low-cost sustainable fuel ethanol. Moreover, selection of a low-cost efficient pretreatment method, process simulation, unit integration, state-of-the-art in one pot saccharification and fermentation, system microbiology/ genetic engineering for robust strain development, and comprehensive techno-economic analysis are all major bottlenecks that must be considered for long-term ethanol production in the transportation sector.