In order to decarbonize the rail industry, the development of innovative locomotives with the ability to use multiple energy sources, constituting hybrid powertrains, plays a central role in transitioning from conventional diesel trains. In this paper, four configurations based on suitable combinations of fuel cells and/or batteries are designed to replace or supplement a diesel/overhead line powertrain on a real passenger train (the Hitachi Blues) tested on an existing regional track, the Catanzaro Lido−Reggio Calabria line (Italy), managed by Trenitalia SpA. (Italy). The configurations (namely battery−electrified line, full-battery, fuel cell−battery−electrified line, and fuel cell−battery) are first sized with the intention of completing a round trip, then integrated on board with diesel engine replacement in mind, and finally occupy a portion of the passenger area within two locomotives. The achieved performance is thoroughly examined in terms of fuel cell efficiency (greater than 47%), hydrogen consumption (less than 72 kg), braking energy recovery (approximately 300 kWh), and battery interval SOC.