Residual biomass is a renewable resource with attractive characteristics to produce energy and biofuels. Diverse studies have stated that residual biomass used for biofuels and energy production can contribute partially to solve the energy demand problem, decreasing fossil fuels carbon emissions. Most works have focused on developing new technologies, processes, and processing systems based on biomass. Other works have addressed the supply chain-planning problem to determine optimal locations considering diverse objectives. A third group of works have proposed schemes based on Geographic Information Systems (GIS) to determine suitable locations in different types of systems. Nevertheless, works capable to combine the advantage of GIS, mathematical programming, and process design have not been properly conducted. Therefore, this paper presents a sequential approach for the optimal planning of a residual biomass processing system. The methodology considers selecting potential locations through a multicriteria methodology based on GIS. Also, this paper proposes a mathematical programming approach for the optimal planning of a residual biomass processing system, which considers as input the locations predefined by GIS methodology, as well as six potential products, six processing routes, and eight raw materials. The mathematical programming approach consists of mass balances to obtain the interconnections between the different supply chain nodes, as well as constraints to model the considered technologies involving capital investment and production costs. The GIS approach was applied to a case study in Mexico, which produced 764 harvesting sites and 334 processing plants for all considered residual biomass types. The optimization approach conducted used 33 processing plants, 467 harvesting sites, and 2 products from 3 biomass types in order to determine the final supply chain topology. Results show that the proposed methodology is a useful tool to determine the optimal supply chain topology during the decision process.