Lignocellulosic biomass (LCB), rich in cellulose, hemicellulose, and lignin, is a renewable and valuable bioenergy source within the circular economy. Lignin, which constitutes 15–40% of the dry weight of lignocellulosic biomass, remains largely under-utilized, as merely 1–2% of the ~50 million tons generated annually is converted into value-added products. Convergent biorefinery strategies facilitated by in silico calculation and microbial engineering are an essential part of research. New pretreatment methods, such as steam explosion, acid hydrolysis, and enzymatic saccharification, enable the effective conversion of biomass into fermentable sugars. A sequential pretreatment strategy combining steam explosion and extrusion yielded 84% glucan, 91% hemicellulose, and 87% lignin recoveries from barley straw. Optimization of microbial pathways is enabled by genome-scale metabolic models (GEMs) and flux balance analysis methodologies. Integration of omics technologies (transcriptomics, genomics, proteomics, metabolomics) with machine learning and systems biology tools is promoted as a revolutionary hypothesis to speed up strain design and bioprocess optimization. Circular economy strategy is adopted through process integration, carbon recycling, and lignin valorization strategy for minimum waste and maximum life cycle sustainability. This chapter presents a conceptual model integrating microbial engineering and computational approaches for circular, sustainable, zero-emission biorefinery design.