Modern diesel engines manufactured for commercial vehicles are calibrated to meet EPA emissions regulations. Many of the technologies and strategies typically incorporated to meet emissions targets compromise engine performance and efficiency. When used in military applications, however, engine performance and efficiency are of utmost importance in combat conditions or in remote locations where fuel supplies are scarce. This motivates the study of the potential to utilize the flexibility of emissions-reduction technologies toward optimizing engine performance while still keeping the emissions within tolerable limits. The study was conducted on a modern medium-duty International V-8 diesel engine with variable geometry turbocharger (VGT) and exhaust gas recirculation (EGR). The performance-emissions tradeoffs were explored using design of experiments and response surface methodology. Then the newly acquired insight is utilized to demonstrate the benefit of dual use strategies that incorporate optimal use of injection timing, injection pressure, VGT setting, and pilot injection. The methodology enables optimizing the engine operation for different objectives, such as minimum emissions or maximum efficiency, and subsequent development of a “best compromise” that improves the fuel efficiency while maintaining emissions within the regulation constraints, but without the use of EGR. Potential elimination of cooled EGR is very significant in dual-use applications, as it reduces the total heat rejection and alleviates packaging difficulties.