In the domain of aerospace engineering, the design of scientific payload instruments for spaceborne applications presents a significant challenge due to the inherent complexity arising from multi-physics phenomena and the associated modeling requirements. Simulating these interdependent physical processes necessitates the implementation of intricate numerical models, often leading to computationally expensive calculations across disparate temporal and spatial scales. Integration of these multi-physics models is the key to understand how the different physics processes affect each other. Furthermore, only optimal efficiency of these coupled physic models enables whole domain simulations to validate the models and integrate them in the tools. In this work we describe the role of the high fidelity computer-aided engineering (CAE) multi-physics in the National Institute of Astrophysics (Institute of Space Astrophysics and Planetology (IAPS)/Italian National Astrophysics Institute (INAF)), the design solutions adopted for the most important thermo-mechanical design drivers for two different kind of space missions: the Large Area Detector (LAD) module that will mount on the enhanced X-ray Timing and Polarimetry (eXTP) mission, a major project of the Chinese Academy of Sciences (CAS) and China National Space Administration (CNSA) currently performing a phase B study and proposed for launch in 2028, and the payload of CUbesat Solar Polarimeter (CUSP), a project of the Institute, funded by the Italian Space Agency (ASI) for a phase A study that consists in a constellation of two CubeSats 6U orbiting around the Earth to measure the linear polarization of X-rays of solar flares in order to improve the knowledge of these violent phenomena.