Methanol as an alternative liquid fuel has a high thermodynamic efficiencies and relatively low environmental impacts. Biomass and municipal solid waste can be considered as feedstock for gasification and further syngas production and methanol synthesis. This work presents an optimization-based process synthesis framework for coal and municipal solid waste to methanol. First, the monomer components of coal and biomass is determined using the proposed model based on the ultimate analysis and proximate analysis data. Next, the pyrolysis zone has been mathematically modeled with an optimization-based monomer model. Then, the pyrolysis, oxidation, and reduction zones are defined with different chemical reactions and equations in which some extents of these reactions are not known a priori. The unknown gasification parameters are obtained to match the experimental gasification results in the best possible way using a nonlinear parameter estimation approach. Finally, based on the optimized gasifier model, process synthesis of coal and municipal solid waste to methanol is formulated as a mixed integer nonlinear model. A sensitivity analysis of the prices of coal and biomass is performed to investigate its efforts on the economic feasibility. The results suggest that a generic MSW gasifier mathematical model can be obtained in which the average error is 8%. A mixture of biomass and coal is of major importance for the transition of coal-to-methanol production.