Given the increasing globalization and industrialization, the worldwide demand for energy continuously increases. In the context of modern Smart Grids, especially small and distributed power plants are a key factor. The present article essentially focuses on the investigation of different approaches for waste heat recovery (WHR) in small-scale CHP (combined heat and power) applications with an output range of approximately 20 kW. The engine integrated into the CHP system under investigation applies a lean-burn combustion process generally providing comparatively low exhaust gas temperatures, thus requiring a careful design that is crucial for efficient WHR. Therefore, this article presents the development and use of a simulation environment for the design and optimization of WHR in small-scale CHP applications. The MATLAB-based code allows various combinations of specific components (e.g., heat exchangers and pumps, as well as turbines and compressors) in different thermodynamic cycles. The focus of this article essentially lies on the comparison of the Joule-Brayton and the Clausius-Rankine cycle regarding operating characteristics as well as the selection of specific working fluids. For the Brayton cycle, the working fluid’s heat capacity and molar mass mainly define feasible operation ranges. Among the working fluids taken into consideration, ammonia indicates the highest potential adding approximately 10% effective net power and increasing the electrical efficiency by about 2%-pts. The Rankine cycle (RC), however, mainly depends on the working fluid’s evaporation. Here, organic working fluids and refrigerants, respectively, indicate highest potentials adding about 19% net power and increasing electrical efficiency by approximately 3%-pts. For applications mainly requiring additional thermal energy, the RC using, for example, ethanol as working fluid provides heated water at temperature levels covering the potential consumption of single households. The Brayton cycle using, for example, ammonia as working fluid, however, allows the feeding of heated water into a district heating grid.