Plasma gasification (PG) based tri-generation process for dimethyl ether (DME) and power generation has been developed to valorize the poultry litter with an objective of energy, exergy, emergy, economic, and environment (5E) sustainability. PG process has been optimized by the application of a radial basis function surrogate optimization algorithm. Comparative analysis of the base and the optimized process has been performed. The results reveal that the economic performance of the optimized process is better than base process with 6% additional DME generation. The energy efficiencies of the optimized process and the base process are 44% and 48%, respectively while there is no significant difference in the results of exergy analysis. Process thermal energy has been converted into electrical energy through steam turbine powered generator, and 1271 kW electricity can be produced through it. Emergy analysis indicates that the sustainability index of the process is 2.509, to some extent, which means that the process is sustainable. Finally, the economic analysis shows that the capital payback period of the optimized process (7.2 year at 70% process efficiency) is shorter while the base process is not feasible when the process efficiency is below 90%. Therefore, this PG tri-generation optimized process is a feasible solution for biomass waste valorization based on 5E analysis.