This dissertation proposes a framework in support of biomass supply chain network design. This framework relies in the use of trucks for short distance biomass transportation, and relies in the use of rail for long-haul, and high-volume transportation of densified biomass. A hub and spoke network design model is proposed for the case when biomass is shipped by rail. These models are created and solved for the following problems: 1) designing a biomass supply chain to deliver densified biomass to a coal fired power plant for coiring and 2) designing biomass-to-biorefinery supply chain using rail for long-haul, and high-volume shipment of densified biomass under economic, environmental, and social criteria. The first problem is modeled as a Mixed-Integer Linear Programming (MILP). A Benders’ decomposition-based algorithm is developed to solve the MILP model because its large size makes it difficult to solve using CPLEX. The numerical analysis indicates that the total unit transportation cost from the farm to a coal plant is $36/ton. Numerical analysis also indicates that biomass cofiring is cost efficient compare to direct coal firing if the renewable energy production tax credit is applied and biomass is located within 75 miles from a coal plant. The second problem is also modeled as a MILP mode. This MILP identifies the number, capacity and location of biorefineries needed to make use of the biomass available in the region. A case study is created using data from a number of States in the Midwest USA. The numerical analysis show that 24.38%-26.12% of the target cellulosic biofuel set by the Energy Independence and Security Act of 2007 can be met at delivery cost $4.01 to $4.02 per gallon. The numerical analysis also reveals the tradeoffs that exist among the economics, environmental impact, and social objectives of using densified biomass for production of biofuel. Finally, this dissertation presents a detailed analysis of the rail transportation cost for products that have similar physical characteristics to densified biomass and biofuel. A numbers of regression equations are developed in order to evaluate and quantify the impact of important factors on the unit transportation cost.