Flexible metal-polymer multilayer structures have become essential elements of modern 21st century technologies, enabling complex functionalities and operation in challenging environments. The downside of the multilayer design is that individual layers complexly interact and the structure tends to adopt the failure mechanism of its most brittle component. Brittle fracture is seldom favorable and the current lack of understanding of multilayer deformation endangers the mechanical integrity of flexible multilayer designs. In this thesis, the simplest multilayer geometry, namely, metallic bi-layers on flexible polymer substrates, is systematically investigated with in situ uniaxial fragmentation to improve the understanding of multilayer-interactions. Special emphasis is put on the influence of brittle layers in different geometric configurations (brittle-ductile: Cr-Au vs. ductile-brittle: Ag-Inconel), using the example of a brittle adhesion layer and a brittle corrosion protection overcoat, as well as control experiments of ductile double-layers (Al-Al) without brittle components. Well established in situ characterization methods from the field of flexible electronics were used to assess the integrity of the bi-layer designs for extreme space and terrestrial applications, including satellite insulation and flexible electronics. Combined in situ surface imaging, resistance measurements and X-ray diffraction revealed that a brittle layer at any position is detrimental to the mechanical behavior of the bi-layer system, unless the ductile layer has a sufficient thickness to allow for significant plastic deformation. The formation of through thickness cracks induced by the brittle component was observed in all ductile layers at very low strains compared to ductile single or double layers. In all cases fracture of the ductile layer had fatal consequences on application-relevant material properties and the design was considered unsuitable for the designated applications. The material system with the best mechanical performance (ductile Al double-layer) was selected for thorough interfacial investigations as a function of thermal treatments, including adhesion energy (tensile induced delamination), interface chemistry (X-ray photo electron spectroscopy) and interface structure (transmission electron microscopy). It revealed an amorphous 3.6 nm interlayer between Al and the polymer, responsible for the good mechanical and interfacial performance. Thermal treatments, which are common heat loads for flexible applications need to be critically assessed. While the Al-PI interface can withstand thermal cycling of +/- 150°C up to 200 cycles without changes, annealing at 300°C for 140 h induced a growth of the interlayer and a change in the interfacial failure mechanism. All findings of this thesis are applicable to the continuously growing field of flexible thin film applications, helping to avoid faulty design and to fabricate reliable flexible devices.