This paper proposes a new general systematic approach for the design of optimal pathways for a biorefinery. The approach includes a set of sequential steps for the superstructure generation and a set of disjunctive programming models for the pathway optimization. The approach allows identification of optimal biorefinery configurations for a given criterion (for example the economic, environmental, or safety, etc). The proposed approach allows the user to solve easily (through a set of subproblems) a difficult problem, and it can be applied to any case study; in this paper, it is applied to a case study for the optimization of the bioalcohols production from lignocellulosic biomass, and the best economic route identified corresponds to the use of biomass using mixed-culture fermentation to yield ammonia carboxylates, then to obtain ester via esterification and finally to obtain the bioalcohols via hydrogenolysis with a cost of $15.14/GJ.