In current production natural gas/gasoline bi-fuel vehicles, fuels are supplied via port fuel injection (PFI). Injecting a gaseous fuel in the intake port significantly reduces the volumetric efficiency and consequently torque as compared to gasoline. In addition to eliminating the volumetric efficiency challenge, direct injection (DI) of natural gas (NG) can enhance the in-cylinder flow, mixing, and combustion process resulting in improved efficiency and performance. A computational fluid dynamics (CFD) approach to model high-pressure gaseous injection was developed and validated against X-ray data from Argonne?s Advanced Photon Source. NG side and central DI of various designs and injection strategies were assessed experimentally along with CFD correlation. Significant effects on combustion metrics were quantified and explained via improved understanding of the in-cylinder flow effects due to NG injection. On-demand in-cylinder blending using E10 PFI and NG DI provides an additional lever to adjust in-cylinder turbulence as well as knock resistance across the engine speed and load range. NG DI improves part-load dilution tolerance due to higher in-cylinder turbulence and the high knock resistance of NG compared to E10 improves wide open throttle (WOT) performance while enabling increased compression ratios (CR). Vehicle level simulations suggest that implementing this strategy on a � ton pick-up truck with a naturally aspirated engine at 12.5:1 CR improves energy consumption on the aggressive US06 drive cycle by 15.5% compared to E10 operation, and gives a petroleum reduction of 78% over the blended range. There are challenges regarding market acceptance and widespread adoption of dual-fuel NG-gasoline vehicle applications beyond the performance degradation when the vehicle runs out of natural gas. Furthermore, those challenges include practical concerns such as loss of cargo volume and payload due to the NG storage tank, extended NG refueling times, fueling convenience due to gasoline and NG fuel tanks, and limited NG fueling infrastructure.