This paper proposes a multi-fidelity and multi-disciplinary framework that combines low- and high-fidelity aerothermodynamics, thermal analysis, flight dynamics, and structural analysis in a modular approach to achieve a favourable trade-off between cost and accuracy. The novelty in the current study is two-fold: one is to simulate a more accurate destructive re-entry process over using a prescribed altitude trigger for fragmentation, and the other is to implement automatic fidelity switches between high- and low-fidelity models for the aerothermodynamics based on the shock-envelope approximation of Billig's formulation. For the high-fidelity flow modelling, the open-source SU2-NEMO code is used to solve the slip to continuum regimes while the SPARTA-DSMC solver is used for transitional and free-molecular regimes. To estimate the fragmentation altitude, a linear structural analysis of objects modelled as joints are continually carried out using the FEniCS finite elements solver. A temperature-dependent von Mises yield criterion is used to identify failure in joints. The software framework, TITAN Transatmospheric Flight Simulation, is applied to the ESA ATV re-entry and fragmentation test case.