This study developed microstructure-based finite element (FE) models to investigate the behavior of cold-sprayed aluminum-alumina (Al-Al2O3) metal matrix composite (MMCs) coatings subject to indentation and quasi-static compression. Based on microstructural features (i.e., particle weight fraction, particle size, and porosity) of the MMC coatings, representative volume elements (RVEs) were generated by using Digimat software and then imported into ABAQUS/Explicit. State-of-the-art physics-based modelling approaches were incorporated into the model to account for particle cracking, interface debonding, and ductile failure of the matrix. This allowed for analysis and informing on the deformation and failure responses. The model was validated with experimental results for cold-sprayed Al-18 wt.% Al2O3, Al-34 wt.% Al2O3, and Al-46 wt.% Al2O3 metal matrix composite coatings under quasi-static compression by comparing the stress versus strain histories and observed failure mechanisms (e.g., matrix ductile failure). The results showed that the computational framework is able to capture the response of this cold-sprayed material system under compression and indentation, both qualitatively and quantitatively. The outcomes of this work have implications for extending the model to materials design and under different types of loading (e.g., erosion and fatigue).