Background: Energy systems for smart regions will require on the one hand a much higher share of renewable energy sources for heat and electricity and on the other hand a high standard integration of industry and utilities supplying households and businesses. As energy options become more diverse, integration of industry into the energy provision for settlements and vice versa become important from an economic and ecological point of view. A particular problem is the supply of bio-energy to large industrial complexes as this requires considerable efforts to manage resource provision as well as constructing smart systems to utilise available resources without posing direct competition to the supply of food and feed. Methods: This paper will discuss the application of Process Network Synthesis (PNS) using the P-Graph method as a tool to generate optimal energy systems supplying industry with energy based on bio-resources in the context of a rural region and small urban centre. Application of these methods to a real life case study in an industrial city in rural context (Weiz in Austria) will be discussed from the viewpoint of general lessons to be learned from the design of complex energy systems linking different energy provision sources to supply industry and residential areas in a systemic way with energy. Results: The synthesis resulted in a basic optimal solution containing the economically most feasible regional energy-technology network. Scenarios show differences in resource use and the creation of revenue. Anaerobic digestion, CHP and wood gasification appear for most of the scenarios.