Sub-scale Flight Testing (SFT) is potentially useful in predicting aircraft flight behaviour, especially in the case of unconventional designs for which legacy information is unavailable and wind tunnel tests are unable to predict aircraft dynamics. A necessary condition for SFT is the design of properly scaled models. However, even in case of perfect scaling, the sub-scale model needs adequate flight performance and handling qualities to enable the execution of flight tests. Thus, the (static and dynamic) stability and control (S&C) and handling qualities (HQ) of sub-scale designs should be evaluated accurately as well as quickly, to allow conceptual design iterations. To this purpose, we propose the use of a 3D panel method (3DPM) for the generation of the non-linear aerodynamic database, in combination with a non-linear flight dynamics analysis. Two main challenges affect the proposed approach. The first concerns the validity of the low-fidelity 3DPM data for the assessment of the sub-scale design S&C and HQ. The second is about the time consuming and error-prone pre/post-processing activity demanded by the hundreds of analysis cases for the aerodynamic database generation. The first issue is investigated by predicting the longitudinal S&C performance and HQ of a sub-scale design using 3DPM analysis and comparing them with the prediction from wind-tunnel test (static) data supplemented by (dynamic) data from 3DPM. Both models appear trimmable and stable and the difference in their HQ are quantified, thus verifying the suitability of 3DPM analysis for sub-scale design assessment. The pre/post-processing challenge is tackled by the development of a knowledge-based engineering application to automate the aerodynamics database generation, reducing the time needed for geometry modeling, discretization and postprocessing of hundreds of cases from weeks to hours. The proposed methodology and its flexibility are demonstrated in this paper, where a commercial 3DPM code and an in-house developed non-linear flight dynamics analysis tool have been used to assess two sub-scale designs, one conventional and one based on the box-wing configuration.