This study conducted mild organosolv pretreatment of sugarcane bagasse with acetone/phenoxyethanol/water (APW) solutions to improve sugar production in the subsequent enzymatic hydrolysis step. The Box–Behnken design was used to optimize pretreatment conditions based on lignin removal. Further examination of the data revealed that lignin removal was positively correlated (R² > 0.95) with the combined severity factor (CSF). Pretreatment under the optimal conditions (125 °C–120 min, 0.17 M H₂SO₄, liquid–solid ratio of 15) led to 98.1% lignin removal and 74.5% cellulose digestibility compared to a low digestibility of 9.3% with raw sugarcane bagasse (SCB). Moreover, the APW process showed effective fractionation of pine, corn stalk and bamboo, and lignin removal was over 90%. The recovered lignin was characterized by 2D-HSQC NMR and ³¹P NMR, suggesting that the pretreatment resulted in breakage of β-O-4, total phenolic OH and H-units increased. However, the enzymatic hydrolysis efficiency (EHE) of samples with a lower lignin content (<4%) varied significantly. Correlations between various substrate-related factors of the pretreated SCB and EHE were analyzed to understand this observation. The results showed that the surface area of cellulose, lateral order index, CrI, and specific surface area were the predominant factors for enzymatic hydrolysis rather than lignin properties.