Thermoelectric generators offer a solution with low complexity and a competitive cost-benefit ratio compared to other efficiency technologies. In this research study, a holistic modelling approach that includes all vehicle interactions is used. The objectives of the study are conventional heavy-duty diesel vehicles and natural gas vehicles. In the context of the transformation of the transport sector, the potentials for future powertrains, such as hydrogen combustion engines and fuel cells, are also presented. The holistic approach enables the evaluation of the technology based on fuel and emission reduction as well as payback time for current and future commercial vehicles. The use of a thermoelectric generator appears to be techno-economically advantageous for current and future powertrains. A differentiation is made between a TEG that is optimized in terms of TCO (TCOmin) and one that is designed to minimize fuel consumption (BSFCmin). For the reference route Stuttgart-Hamburg-Stuttgart (SHHS), the average fuel savings for a current diesel vehicle with a load of 40 t are 1.0 % for the TCOmin variant and 1.2 % for the BSFCmin variant. Analogously, the payback periods are 2.0 and 3.1 years, respectively. For current natural gas vehicles, the fuel savings are 2.1% for the TCOmin and BSFCmin variants. The payback periods are 1.4 and 1.5 years, respectively. Thereby, the fuel savings represent a significant increase of the state of the art. For the payback period, an analysis is carried out for the first time. The thermoelectric waste heat recovery technology is of interest for vehicle applications with gasoline, diesel, natural gas, hydrogen combustion engines and fuel cells. Here, the use of a TEG in combination with liquid hydrogen shows the greatest potential. In addition to energy recovery and the supply of electrical energy, the TEG relieves the challenging cooling system of PEM fuel cells. © 2023 The Authors.