The transition to sustainable bioeconomy models has intensified interest in lignocellulosic biomass hydrolysis as a pathway for renewable energy and bioproduct generation. This chapter offers a comprehensive comparative analysis of batch, fed-batch, and continuous reactor configurations in the enzymatic hydrolysis of lignocellulosic feedstocks, emphasizing how reactor design, pretreatment strategies, and feedstock characteristics collectively influence process performance. Batch systems, while prevalent in laboratory-scale research due to their operational simplicity, face significant scalability constraints. Fed-batch configurations mitigate these challenges by enabling gradual substrate addition, which enhances hydrolysis efficiency and process flexibility. Continuous reactors, though complex and capital-intensive, offer the greatest potential for industrial integration and alignment with circular bioeconomy principles due to their high productivity and steady-state operation. The chapter further explores the interplay between pretreatment methods—such as acid, alkaline, and organosolv—and reactor design, showing the necessity of integrated system optimization. By synthesizing recent literature and evaluating industrial trends, the chapter advances the understanding of reactor-preprocessing compatibilities and provides strategic insights for the development of scalable and sustainable biorefineries.