We propose a superstructure optimization framework for process synthesis with simultaneous heat integration and utility plant design. Processing units in the chemical plant can be modeled using rigorous unit models or surrogate models generated from experimental results or off-line calculations. The utility plant subsystem includes multiple steam types with variable temperature and pressure. For the heat integration subsystem, we consider variable heat loads of process streams as well as variable intervals for the utilities. To enhance the solution of the resulting mixed-integer nonlinear programming models, we develop (1) new methods for the calculation of steam properties, (2) algorithms for variable bound calculation, and (3) systematic methods for the generation of redundant constraints. The applicability of our framework is illustrated through a biofuel case study which includes a novel non-enzymatic hydrolysis technology and new separation technologies, both of which are modeled based on experimental results. (C) 2016 Elsevier Ltd. All rights reserved.