The industrial applicability of exotic and wild fruits has been investigated as stand-alone processes framed to obtain a single main product. However, their combination and the valorization of the processing residues in a biorefinery scheme have not been explored. Therefore, this work aims to assess the technical and economic feasibility of low-scale biorefineries based on annatto and açai as raw materials. Therefore, the actual processing of both fruits was carried out experimentally. For annatto, the extraction of dye paste was performed, obtaining mass yields of up to 58.4% by working with ground seed. Regarding the açai, pulp was obtained with a polyphenol content of 23.56 mg of gallic acid equivalent per gram of sample. The residues generated in both processes were used as substrates for biogas production, achieving biomethane yields between 186–533 mL per gram of volatile solids. These results were the basis for the design and simulation of process scale-up in low-scale biorefinery contexts. Five scenarios were evaluated, involving the production of annatto dye paste, açai pulp, biogas from exhausted annatto seeds, slurry and seeds of açai, and feedstock integration. As the main energy result, it was found that the individual production of açai pulp can fully supply the required energy of the process through the self-generation index. From the economic perspective, it was found that there is economic feasibility working with flows below the regional and national production in Colombia for all scenarios.

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