Climate change, along with the growing need to reduce greenhouse gases (GHG) emissions and eliminate the use of fossil fuels, as well as the corresponding societal challenges, are the key drivers behind the adoption by the European Union of several approaches for the development of the concepts of Circular Economy and Bio-economy. These latter aim at promoting new strategies and policies, thus contributing to a more viable social, financial and technological model. Among the priority areas of the EU Circular Economy Action Plan, the reuse of food waste is a key issue, promoting the transition to a more sustainable scheme. The valorisation of food processing by-products and their transformation into a spectrum of marketable products (food, feed, materials, chemicals) and energy (fuels, power, heat), has been enhanced by the integrated “biorefinery concept” through several different policies and funding opportunities. However, the variability in quantity and composition of residual streams, as well as the lack of information regarding the operation and viability of the bio-industries, render the management of the residual streams rather challenging. Towards this direction, the European project Model2BIO develops and validates an innovative model-based decision support tool that predicts the physico-chemical characteristics of the residual streams generated in the agrifood sector, explores all the available alternatives for their valorization as feedstock in the bio-industry and selects the most appropriate options considering social, economic, environmental and regulatory criteria (including logistics). The Region of Western Macedonia serves as one of the test beds for the development of the tool, since it has significant potential in agricultural, dairy and wine-making sectors’ residues, the majority of which remains unexploited. In this context, the present study aims to detect and report the existing agri- food (meat, cheese, wine and pepper) and bio-based industries, in order to determine several parameters of the residual streams (type, volume and physicochemical characteristics) and to assess the sustainability of a biorefinery in the area. Considering the transitional period Western Macedonia undergoes since 2020 due to the termination of the lignite mines operation for power production, such a venture would be of a high importance for the Region, which prioritizes alternative, greener and more sustainable pathways.