A tri-generation-based sustainable poultry litter (PL) valorization process has been developed in this study. To make the proposed process economically viable and energy efficient, the primary gasification process of PL is further enhanced to convert syngas into dimethyl ether (DME). According to our energy analysis, the current tri generation process exhibits 57% energy efficiency, which is 12% higher than that of PL gasification (45%). A particle swarm optimization (PSO)-based algorithm was applied to optimize the gasification and DME production process. According to PSO results, the optimum operating conditions are 667 ◦C, 2 bar, and 1.78 air ratio in the gasification process, while using reaction temperatures of 400 and 100 ◦C in the DME reactors leads to 242.6 kg/ ton DME with 4414.6 kJ/s net heat. On the contrary, only 190.8 kg/ton DME with 4642.2 kJ/s net heat can be generated in the base process. The optimized process is economically viable to achieve an 80% plant operational efficiency with an internal rate of return (IRR) of 16.3% when compared with the base process, which becomes infeasible when the plant efficiency is <90%. A sustainability index (SI) was developed, and the results show that the optimized process was more sustainable (0.290) than the base process (0.279). Therefore, our optimized DME process is more economically viable and eco-friendly