The DOE Co-Optima initiative has a focus on investigating the ability of fuel properties to work in tandem with advanced combustion engines to increase fuel economy. Advanced compression ignition strategies like spark assisted compression ignition (SACI) and partial fuel stratification (PFS) have been shown to achieve better efficiency and emissions performance than traditional combustion processes (i.e., conventional diesel combustion, spark ignited combustion). These strategies rely on a high degree of fuel mixing and a globally dilute environment to achieve lower temperature combustion. The avoidance of fuel rich regions and the reduction in peak flame temperatures result in low soot and NOx formation. Despite their clear benefits, operating range limitations have been identified for all combustion strategies. The limitations stem from the fundamental characteristics of each combustion process, hence they can't be entirely avoided. These limitations are also geometry, fuel type, dilution level and mixture preparation dependent. In practical applications, engines have to operate over a wide range of conditions, which associated with the inherent limitations and benefits of each combustion mode, suggests that an optimal solution is an engine capable of operating across multiple combustion modes. Metal engine experiments have been conducted on a single-cylinder research engine equipped with variable valve actuation and a 12.5:1 compression ratio, more appropriate for high load boosted spark ignition operation. Five fuels with different chemical class compositions but matched research octane number (RON) were tested under both SACI and PFS at mid load conditions. Spark and injection timings were varied for SACI and PFS, respectively, to assess their control sensitivity over the heat release rate and their impact to engine efficiency and emissions. Fuel chemistry effects on the performance of each combustion mode are then discussed in the context of multi-mode engine operation.