<p>Lignocellulosic biomass (LCB), composed of cellulose, hemicellulose, and lignin, offers a sustainable alternative to fossil fuels through cellulose valorization. However, strong interpolymer interactions within the plant cell wall contribute to biomass recalcitrance, complicating cellulose extraction and reducing process efficiency. This review explores microstructural insights from molecular dynamics simulations, which elucidate the effects of structural motifs, solvent environments, and thermal conditions on cellulose accessibility. The insights derived from such studies can be used to design effective cellulose extraction strategies. This review critically examines conventional, advanced, and combined extraction strategies, emphasizing how process parameters and biomass characteristics influence cellulose recovery and purity. Also, optimization of different cellulose extraction methods and analytical characterization techniques for extracted cellulose has been discussed. Combining complementary techniques, guided by both simulation and empirical data, can offer the most effective path toward selective, high-yield cellulose isolation. Collectively, this multi-scale perspective informs the design of adaptable and resource-efficient bioprocessing strategies.</p> Graphical Abstract <p></p>