Panela is the second most important rural agro-industry after coffee in Colombia. This agro-industry produces a large amount of bagasse from non-centrifugal sugar (B-NCSP) without valorization. B-NCSP is used in combustion boilers in panela production, causing greenhouse gas emissions and health problems. This research aims to compare the sustainability of two B-NCSP biorefineries considering the current residue use. The sustainability of the biorefinery scenarios was analyzed to promote rural economic development in Colombia. In both biorefinery scenarios, biogas was evaluated as an energy vector to meet the energy demand of panela production. Two biorefinery scenarios were considered: (i) saccharification, bioethanol, and biogas production and (ii) acid pretreatment, saccharification, xylitol, bioethanol, and biogas production. Experimental data of the pretreatment, saccharification, and anaerobic digestion stages were used as input information in simulations. Technical, economic, environmental, and social metrics were used to estimate a sustainability index. The experimental glucose yield in scenario 2 was 0.42 ± 0.03 (31.52 ± 2.36 g/L) g/g B-NCSP, 1.8 times greater than scenario 1. The biogas yield in scenario 2 was 504.23 ± 21.68 (71.16% CH4) L/kg B-NCSP, 3.3 times greater than scenario 1. Scenario 1 was unfeasible at different scales. Xylitol production helps to improve the economic feasibility in scenario 2 since the payback period was 15 years. This scenario can create 36 job positions with a wage 18% higher than the minimum wage in Colombia (highest sustainability index of 72.44%). Finally, biogas produced in scenario 2 supplies 62.76% of the energy demand needed in the panela production process, reducing the environmental impact.