The reduction of both harmful emissions (CO, HC, NOx, etc.) and gases responsible for greenhouse effects (especially CO2) are mandatory aspects to be considered in the development process of any kind of propulsion concept. Focusing on ICEs, the main development topics are today not only the reduction of harmful emissions, increase of thermodynamic efficiency, etc. but also the decarbonization of fuels which offers the highest potential for the reduction of CO2 emissions. Accordingly, the development of future ICEs will be closely linked to the development of CO2 neutral fuels (e.g. biofuels and e-fuels) as they will be part of a common development process. This implies an increase in development complexity, which needs the support of engine simulations. In this work, the virtual modeling of real fuel behavior is addressed to improve current simulation capabilities in studying how a specific composition can affect the engine performance. The goal is to create a series of models that allow to virtually investigate different fuels and to minimize, as much as possible, the costly and time-consuming experimental tests. In the first part, a fuel modeling approach is presented and compared with traditional methodologies. Subsequently, two fuel virtual investigations are presented. In the first, fuels with different RON and oxygenates content are compared to analyze their knock behavior and performance potential. In the second analysis, the fuel investigation - conducted virtually at the FKFS of Stuttgart and experimentally at the engine laboratory of the Chair of Internal Combustion Engines at the Technical University of Munich with the support from Volkswagen Motorsport GmbH - on a single-cylinder research engine operating with the innovative SACI (Spark Assisted Compression Ignition) combustion concept is presented.