Internal combustion engines (ICEs) have been used in power generation even before they were massively employed for transportation. Their high reliability, excellent power-to-weight ratio, and thermal efficiency have made them a competitive choice as main energy converters in small to medium-sized power plants. Process simulators can model ICE-powered energy plants with limited depth due to the highly simplified engine models used, which require the description of individual energy and mass flows entering or leaving the engine. ICE models available in process simulators are therefore not predictive but merely descriptive representations of the engines. Because the combustion process within the ICE is typically the main cause of exergy destruction in ICE-powered energy plants, a better understanding of the global effects of different engine parameters is desirable. This article presents and exploits the integration of an internal combustion engine simulator with a process simulator, so as to obtain a novel, fully coupled simulation platform to analyze the performance of ICE-based power plants. A simulation model of an actual cogeneration plant is used as an example for the application of the proposed computational methodology. The results show that by manipulating engine mapping parameters the plant overall efficiency can be improved.