The global interest in utilizing waste from agro–industrial processes through the implementation of clean technologies is rapidly increasing. This study evaluates the technical, economic, and environmental feasibility of valorizing regional agro–industrial residues in Santander, Colombia, specifically coffee mucilage, cocoa mucilage, and pig manure, using integrated biorefinery scenarios. Modernizing these processes is essential given a theoretical energy potential of 75,000 TJ/year, which could generate up to 20,833 GWh/year. Three biorefinery scenarios were designed and simulated using Aspen Plus^® to produce bio-hydrogen, methane, and methanol. The total plant capacity was established at 31.7 t/day, distributed according to regional biomass availability: 4.62 t/day of cocoa mucilage, 1.83 t/day of coffee mucilage, and 25.25 t/day of pig manure. The technical results for Scenario 1 indicated a reformed H₂ production of 0.15 t/day with an associated preheating energy requirement of 193,365 kJ/h. Environmental impact assessment using the ReCiPe 2015 Midpoint methodology identified Scenario 3 as having the lowest direct CO₂ mass flow (9.28 t/day) due to carbon consumption during methanol synthesis. However, Scenario 1 reported a CO₂ equivalent (CO₂e) of 194.37 t/day, reflecting indirect emissions from thermal and energy requirements. Economic analysis, validated through engineering cost references, demonstrated that while Scenario 3 offers a diverse product portfolio, it is currently not cost-effective as the production costs exceed the total expected income. Consequently, Scenario 2 is identified as the most balanced alternative for the Santander context, offering a sustainable compromise between technical efficiency, environmental mitigation, and economic viability.