In this study a detailed 1-D engine system model coupled with 3-D computational fluid dynamics (CFD) analysis was used to investigate the air system design requirements for a heavy duty diesel engine operating with low reactivity gasoline-like fuel (RON70) under partially premixed combustion (PPC) conditions. The production engine used as the baseline has a geometric compression ratio (CR) of 17.3 and the air system hardware consists of a 1-stage variable geometry turbine (VGT) with a high pressure exhaust gas recirculation (HP-EGR) loop.The analysis was conducted at six engine operating points selected from the heavy-duty supplemental emissions test (SET) cycle, i.e., A75, A100, B25, B50, B75, and C100. The engine-out NOx target was set at 1 g/hp-hr (1.34 g/kWh) to address a future hypothetical tailpipe NOx limit of 0.02 g/hp-hr (0.027 g/kWh) while an engine-out particulate matter (PM) target of 0.01 g/hp-hr (0.013 g/kWh) was selected to comply with existing EPA 2010 regulations. Closed-cycle 3-D CFD combustion simulation was conducted across the six engine operating points to identify the proper combustion recipe that delivers high fuel efficiency while keeping the NOx and PM within the targets. The air system boundary conditions and combustion heat release profiles were then imposed on a well-validated 1-D GT-Power engine model for the air system development and performance evaluation. In this work we investigated two different air-system configurations: (A) 1-Stage turbocharger (TC) w/ HP-EGR loop and (B) 2-Stage turbocharger w/ HP-EGR loop. To more realistically meet the PPC air-system boundary requirements (Boost, EGR%), the authors modified and incorporated several high efficiency turbocharger maps available in the literature.Based on the 1-D engine modeling results, both the 1-Stage and the 2-Stage turbocharger systems were capable of meeting the air-system requirements for an engine-out NOx target of 1g/hp-hr across the operating points investigated. A detailed energy balance analysis and the combustion physics comparisons between ULSD and RON70 were also discussed.