Production of green chemicals and biofuels in biorefineries is the potential alternative for petrochemicals and gasoline in transitioning of petro-economy into bioeconomy. However, an efficient biomass pretreatment process must be considered for the successful deployment of biorefineries, mainly for use of lignocellulosic raw materials. However, biomass recalcitrance plays a key role in its saccharification to obtain considerable sugar which can be converted into ethanol or other biochemicals. In the last few decades, several pretreatment methods have been developed, but their feasibility at large-scale operations remains as a persistent bottleneck in biorefineries. Pretreatment methods such as hydrodynamic cavitation, ionic liquids, and supercritical fluids have shown promising results in terms of either lignin or hemicellulose removal, thus making remaining carbohydrate fraction amenable to the enzymatic hydrolysis for clean and high amount of fermentable sugar production. However, their techno-economic feasibility at industrial scale has not been yet studied in detail. Besides, nanotechnological-based technologies could play an important role in the economically viable 2G sugar production in future. Considering these facts, in the present review, we have discussed the existing promising pretreatment methods for lignocellulosic biomass and their challenges, besides this strategic role of nano and biotechnological approaches towards the viability and sustainability of biorefineries is also discussed.