The transition toward renewable fuels has increased interest in second-generation bioethanol obtained from lignocellulosic residues. Sugarcane bagasse is particularly attractive because it is produced in large quantities by the sugar industry and contains substantial fractions of cellulose and hemicellulose that can potentially be converted into fermentable sugars. Its utilization, however, is complicated by the highly organized association of cellulose, hemicellulose, and lignin, which restricts enzymatic accessibility and makes pretreatment necessary. Alkaline treatment offers a practical strategy for bagasse because it promotes fiber swelling, disruption of lignin–carbohydrate associations, and partial delignification while preserving much of the cellulose fraction. The carbohydrates exposed after pretreatment must then be converted into soluble sugars through enzymatic saccharification. Trichoderma reesei is an established producer of extracellular cellulolytic and hemicellulolytic enzymes and therefore represents a suitable biological source of enzymes for this stage. Subsequent fermentation presents another difficulty because conventional Saccharomyces cerevisiae efficiently ferments glucose but does not normally utilize xylose effectively, whereas Scheffersomyces stipitis possesses a native xylose-fermenting metabolism. Their combination therefore provides a possible division of metabolic labor between hexose and pentose fermentation. Nevertheless, differences in oxygen requirements, temperature optima, inhibitor tolerance, and growth kinetics make an uncontrolled three-organism culture biologically problematic. This review evaluates a staged process involving alkaline pretreatment, T. reesei-derived enzymatic saccharification, and controlled S. cerevisiae–S. stipitis co-fermentation. Particular attention is given to pretreatment selectivity, inhibitor formation, enzyme composition, mixed-sugar metabolism, oxygen transfer, population stability, process monitoring, ethanol recovery, scale-up, and techno-economic relevance. The available evidence supports the individual functional roles of the three microorganisms and the feasibility of mixed-yeast fermentation, but direct experimental proof of superiority of the complete three-organism sugarcane-bagasse process remains limited. Consequently, the system should be approached as a scientifically testable bioprocess strategy rather than as an already optimized technology
