For more than sixty years, thermoelectric compounds that convert (waste) heat energy to electrical energy based on the Seebeck and Peltier effects have received much attention as energy harvesting devices and power generators. However, the discovery of novel high-performance and environmentally friendly thermoelectric materials remains challenging for large-scale applications. Theory can be used as an alternative approach to accelerate the search. Cluster-based molybdenum chalcogenide compounds will serve as an illustration.