This work compares the fundamental thermodynamic underpinnings (i.e. working fluid properties and heat release profile) of various combustion strategies with engine measurements. The approach employs a model that separately tracks the impacts on efficiency due to differences in rate of heat addition, volume change, mass addition, and molecular weight change for a given combination of working fluid, heat release profile, and engine geometry. Comparative analysis between the measured and modeled efficiencies illustrates fundamental sources of efficiency reductions or opportunities inherent to various combustion regimes. Engine operating regimes chosen for analysis include stoichiometric spark-ignited combustion and lean compression-ignited combustion including homogeneous charge compression ignition, spark-assisted homogeneous charge compression ignition, and conventional diesel combustion. Within each combustion regime, the effects of engine load, combustion duration, combustion phasing, compression ratio, and charge dilution are explored. Model findings illustrate that even in the absence of losses such as heat transfer or incomplete combustion, the maximum possible thermal efficiency inherent to each operating strategy varies to a significant degree. Additionally, the experimentally measured losses are observed to be unique within a given operating strategy. The findings highlight the fact that to create a roadmap for future directions in internal combustion engine technologies, it is important to not only compare the absolute real-world efficiency of a given combustion strategy but also to examine the measured efficiency in context of what is thermodynamically possible with the working fluid and boundary conditions prescribed by a strategy.