The scientific community has developed several tools in the last years that can be used to satisfy the economic- and environmental requirements of the design of a process system. However, tools for the systematic connection and evaluation between design and long- and short term operation is currently still at an infant stage. As design and operation are integrated, the overall complexity of such system increases significantly, ergo, the required computer power and capacities of solution algorithms also do. In our work we develop a systematic framework to assess robustness and sustainability of a process design and the operational strategy of the design involving process intensification. We use a four-step methodology; first we define the objectives and develop suitable process models that describe the process intensification alternative, secondly we execute a response surface methodology to obtain better understanding of how to influence the objectives, thirdly we optimize and select the design alternatives and the operational strategies, and lastly we evaluate the design and operational alternatives.