Reactive multilayer films are a high energy dense configuration for energetics widely studied for various pyrotechnic applications. The objective of this study is to investigate the influence of substrate-induced localized stress on the combustion properties of Al/CuO reactive thin films. Square microbumps are patterned on glass substrates to serve as embedded stressor elements. Stress-induced structural or morphological changes of the materials deposited around the microbumps are characterized using high-magnification transmission and scanning electron microscopy, providing simultaneous nanometer imaging resolution and detailed chemical analysis. The structural and chemical changes (appearance of reactant intermixing and voids) around the microbumps modify the energetic reservoir and the thermophysical properties of the film. The heat of reaction, the flame temperature and the effective thermal conductivity of the film are altered (loss of ~15%), leading to a global decrease in the material reactivity. The flame velocity of the film deposited on the substrate with microbumps drops by 9.2%, 32.4% and 48.7% for microbump heights of 0.15, 0.35 and 0.83 µm, respectively. This work helps deepen the understanding of the effect of stress-induced strain on reactive film combustion properties and provides perspectives for controlling the reaction of reactive thin films by tailoring the strain distributions within the films.