The Flying-V is invented as a sustainable innovation for the aviation industry, promising 20% more fuel efficiency than its benchmark, the Airbus A350. There are many challenges to be addressed to bring the Flying-V to a more developed stage, one of them is the design of the structure that supports both the engine and the landing gear, which motivated this research. The aim of this research was to develop an automated design methodology for unconventional engine mounting structures that can be applied to the Flying-V. For the Flying-V, three concepts were evaluated, and the selected concept is a skin-stiffened ortho-grid box structure that combines the landing gear bay and the pylon functions. A total of 25 load cases are derived from the certification specifications CS-25, from which 7 critical load cases are selected and used for design optimisation. Preliminary dynamic loads for the landing gear are estimated, and the landing gear parameters are optimised by minimising the load acting on the landing gear bay for different landing load cases, including lateral and one-gear landing. Dynamic loads from the engine arising from an imbalance due to different failure scenarios related to fan blades being lost; the worst failure scenario was used in the design. The selected concept is assembled into a parameterised finite element model containing 30 design variables. The design is optimised using a design of experiments created using Latin Hypercube Sampling method. Four failure modes are computed using a combination of finite element outputs and (semi-)analytical equations accounting for structural instabilities. The obtained result is a parameterisation of the primary engine mounting structure of the Flying-V, having a structural mass of 3411 kg per half-wing-fuselage and a minimum margin of safety of 0.09 concerning column buckling of a stiffener. This critical margin of safety is found in the lateral landing load case, which introduces a significant moment on the structure. Moreover, the second most critical failure is produced by the maximum thrust of the engine during take-off.