This paper quantifies the impacts of the airframe configuration change on the performance differences between a tube-and-wing and a blended wing body aircraft. Both are sized for a 5,000 nmi design range carrying 225 passengers, initially using the same engine. Parametric geometry is created for both concepts based on relevant public information. The tube-and-wing notional geometry is derived from the existing Boeing 767-300ER, whereas JetZero’s concept inspires the blended wing body. These geometries are optimised using computational fluid dynamics and gradient-free approaches. Drag polars for each optimised model, spanning the expected operating envelope, are generated using computational fluid dynamics simulations and multi-fidelity surrogate models. Mission analysis is performed for the blended wing body, a conventional tube-and wing variant with metallic structures, and an advanced tube-and-wing with composite structures. The results show that the blended wing body operates with 15-20% higher lift-over-drag during the cruise, 24% lower fuel burn for the design mission, and 15% reduction in ramp weight relative to the conventional tube-and-wing. These differences drop to 20% for the design mission fuel burn and 10% for the ramp weight relative to the advanced tube-and-wing. When the engines are re-sized and optimised separately for each configuration, the blended wing body demonstrates a 25% improvement in block fuel and 16% reduction in ramp weight relative to the conventional tube-and-wing, which decreases to 21% and 10% relative to the advanced tube-and-wing. In both comparisons, the fuel efficiency advantage of the blended wing body decreases as the mission range is reduced.