The present work deals with the biotechnological valorization of the vinasse through a sustainable biorefinery. The aim was to design and analyze, through process simulation, a biorefinery for the valorization of vinasse in products such as organo-mineral fertilizers, supplements for animal feed, and biogas. For this purpose, the SuperPro Designer software was used, and a modified hierarchical decomposition method was applied. One base case and three scenarios were techno-economically assessed, and the net present value was used as a selection criterion. The technological configuration with the best techno-economic criterion was analyzed socially and environmentally. The results suggest that the best configuration of the biorefinery corresponded to scenario 3, with a net present value of USD$73,364,000, a number of direct employees of 38, and a blue water footprint of 16.16 m3/h. These findings highlight the potential of the design of biorefineries to address the valorization of vinasses in Colombia and worldwide.