Reducing energy consumption and emissions in industrial plants in a cost-effective way is of great significance for the sustainability of the process industry as well as for tackling climate change and ensuring national energy security. While major advances towards this goal have been made over the last fifteen years in the process industry, there is a great need, especially in the current financial and energy climate, for another wave of step-change improvements. This calls for a holistic, quantitative and systematic analysis of the current energy and process options to identify sustainable, cost-effective opportunities for energy efficiency in a synergistic manner with business objectives, carbon foot-printing and environmental criteria and operability concerns. In this proposal, the development of a design toolbox for the optimal and sustainable delivery of energy efficiency solutions in the process industry is described. The toolbox comprises generic methodologies and tools for (i) the identification of optimal retrofit/design opportunities for energy efficiency, (ii) the analysis of the process/energy integration opportunities of the process with centralized and distributed energy systems, (iii) the delivery of guaranteed operability for the design options, and (iv) trade-off detailed analysis of the various options regarding cost/profit, energy consumption environmental impact.