The need to reduce carbon dioxide emissions from motor vehicles pushes the European Union towards drastic choices on future mobility. Despite this, the engines of the “future” have not yet been defined: the choice of engine type will undoubtedly depend on the type of application (journey length, availability of recharging/refueling facilities), practical availability of alternative fuels, and electricity to recharge the batteries. The electrification of vehicles (passenger and transportation cars) may be unsuitable for several aspects: the gravimetric energy density could be too low if the vehicle has to be lightweight, must achieve a high degree of autonomy, or needs a very short refueling time. To compare the sustainability of various partially or fully electric propulsion systems equipped with thermal engines powered by alternative fuels (e-fuels, hydrogen, green methane, etc.) or powered by fuel cells, it is necessary to consider the entire life cycle of the vehicle, including the production stage of the “propellant”. This methodology, the well-known Well-to-Miles analysis, is the basis of the energy model presented in this work and developed with Matlab code. The energy model is able to consider the overall energy cost required by a vehicle to complete a specific journey starting from the production of the fuel that powers it (electricity included). The model is validated by comparison with reported carbon dioxide emissions and fuel consumption data for two modern cars, one powered by a petrol engine, the other plug-in. Finally, a comparison between the declared data and the simulation results for a fuel cell vehicle and a pure battery vehicle is reported. The model is a valuable tool for energy assessment (consumption, emissions) of various propulsion units suitable for making a specific trip.