In the design of chemical/energy production systems, a major challenge is how to quantify the sustainability of the systems. Concerns on economic return and environmental impacts have been well received by researchers and practitioners. However, the irreversibility of the process has not been taken into consideration yet. Based on the first and second laws of thermodynamics, exergy analysis allows accounting for irreversibility in the process and provides a detailed mechanism for tracking the transformation of energy and chemicals. Sustainability assessment in the societal dimension is mostly a "soft" activity, as the aspects to be considered and the method of evaluation are frequently subjective. How to assess the societal impact of a process in the early design stage remains as a challenging issue. This paper will present a sustainability assessment method incorporating economic, environmental, efficiency, and societal concerns. The efficiency assessment is conducted through exergy analysis, while the societal concerns are measured by an enhanced inherent safety index method. In conjunction with a multicriteria decision-analysis method, this methodology will provide critical guidance to the designers. The efficacy of this methodology will be demonstrated through a case study on biodiesel production Processes. The results show that the new heterogeneous catalyst process performs better than the traditional homogeneous process in every dimension.