This study explores a new multi-physics, multi-scale in-silico approach aimed at understanding coronary artery disease plaque growth and remodeling. Previous works coupled agent-based models (ABMs) separately with finite element analysis (FEA) [1] or computational fluid dynamics (CFD) [2], [3]. Although useful to study individual contributions of tissue mechanics or hemodynamics to plaque growth separately, a fully coupled multi-physics model has potential to investigate their combined impact. This study presents a novel method that achieves this by merging hemodynamics via CFD, biological processes via ABM, and biomechanics via FEA into a single multi-scale, multi-physics simulation (CAFe) [Figure 1]. A volumetric, 3D tetrahedral mesh represents the vessel geometry with the various cells and molecules modelled as virtual agents. The tetrahedral mesh accurately captures geometrical complexities of coronary arteries while facilitating the application of molecular diffusion equations and a cell migration algorithm. A notable advancement of this approach is the maintenance of spatial and temporal continuity across the different physics domains, ensuring consistency when combined with CFD and FEA. The innovative approach outlined in this study marks a significant step toward predictive multi-physics approaches for more effective and therapeutic strategies in cardiovascular disease management.