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Traditional criteria for designing processes that utilize only economic aspects can have a negative impact on the environment and society. In this study, a process for the production of dimethyl ether (DME) from methanol is evaluated by employing sustainability metrics. Operational conditions are optimized by implementing a rigorous global multi-objective optimization algorithm based on maximization of economic performance measured by the return on investment (ROI) and minimization of environmental and social impacts. The most efficient operational conditions for DME production based on sustainability criteria are obtained with a homotopy continuation method in conjunction with a process simulator. The resulting conditions indicate that the global warming metric of the DME process is decreased more than 10 times and the decrease of photochemical smog formation, mass intensity and energy intensity is 96%, 12% and 9%, respectively. The optimized, sustainable process shows an only an insignificant reduction in terms of economic aspect. [ABSTRACT FROM AUTHOR]