After a brief review of the current research on the production of synthetic natural gas (SNG) from lignocellulosic biomass by gasification and methanation, this paper presents detailed thermo-economic process optimisation of the polygeneration of SNG, power and heat. Based on a previously developed model, all suitable candidate configurations of a superstructure of promising technologies for the individual conversion steps are optimised with respect to the overall efficiency and investement cost with an evolutionary, multi-objective algorithm. In an extensive analysis, the influence of process technology, operating conditions and process integration on the thermo-economic performance is discussed and the best technology matches are determined. Systematically optimised flowsheets might thereby convert 66 to 75% of the dry wood’s lower heating value to SNG while cogenerating a considerable amount of power and/or industrial heat. In order to provide a general database of optimal plant configurations, cost exponents that quantify the economies of scale are regressed, and the most profitable flowsheets are identified for different energy price scenarios and scale. A comparison with current literature on SNG production from biomass reveals the potential of applying such systematic process systems engineering approaches for the design of energy- and cost-efficient biofuel plants.