The huge energy potential of Enhanced Geothermal Systems (EGS) makes them perspective sources of non-intermittent renewable energy for the future. This paper focuses on potential scenarios of EGS development in a locally and in regard to geothermal exploration, poorly known geological setting—the Variscan fold-and-thrust belt —for district heating and cooling of the Göttingen University campus. On average, the considered single EGS doublet might cover about 20% of the heat demand and 6% of the cooling demand of the campus. The levelized cost of heat (LCOH), net present value (NPV) and CO2 abatement cost were evaluated with the help of a spreadsheet-based model. As a result, the majority of scenarios of the reference case are currently not profitable. Based on the analysis, EGS heat output should be at least 11 MWth (with the brine flow rate being 40 l/s and wellhead temperature being 140 °C) for a potentially profitable project. These parameters can be a target for subsurface investigation, reservoir modeling and hydraulic stimulation at a later stage. However, sensitivity analysis presented some conditions that yield better results. Among the most influential parameters on the outcome are subsidies for research wells, proximity to the campus, temperature drawdown and drilling costs. If realized, the EGS project in Göttingen might save up to 18,100 t CO2 (34%) annually.