Biorefinery feasibility is highly influenced by the early design of the best feedstock transformation pathway to obtain value-added products. Pretreatment has been identified as the critical stage in biorefinery design since proper pretreatment influences subsequent reaction, separation, and purification processes. However, many pretreatment analyses have focused on preserving and valorizing six-carbon sugars for future use in bioconversion processes, leaving aside fractions such as hemicellulose and lignin. To date, there has been no pretreatment systematization for the removal of lignocellulosic fractions. This work defines pretreatment efficacy through operational, economic, environmental, and social indicators. Thus, using the data reported in the literature, as well as the results of the simulation schemes, a multi-criteria weighting of the best-performing schemes for the isolation or removal of cellulose, hemicellulose, and lignin was carried out. As a main result, it was concluded that dilute acid is the most effective for cellulose isolation and hemicellulose removal for producing platform products based on six- and five-carbon sugars, respectively. Additionally, the kraft process is the best methodology for lignin removal and its future use in biorefineries. The results of this work help to elucidate a methodological systematization of the pretreatment efficacy in the design of biorefineries as an early feasibility stage considering sustainability aspects.