Many devices in electronics are in the form of multilayered structures. These structures can fail catastrophically if they contain defects or cracks. Enhancing their fracture properties is therefore critical to improve the reliability of the systems. The interface-dominated fracture mechanics of multilayered structure was studied using experiments and finite element (FE) modeling by considering two examples: thin films on polymer substrates in flexible electronics and Cu leadframe/epoxy molding compound (EMC) in micro-electronics packaging. In the first example, aluminum-manganese (Al-Mn) thin films with Mn concentration up to 20.5 at.% were deposited on polyimide (PI) substrates. A variety of phases, including supersaturated fcc (5.2 at.% Mn), duplex fcc and amorphous (11.5 at.% Mn), and completely amorphous phase (20.5 at.% Mn) were obtained by adjusting alloying concentration in the film. In comparison with crystalline and dual phase counterparts, the amorphous thin film exhibits the highest fracture stress and fracture toughness, but limited elongation. Based on a fracture mechanism model, a multilayer scheme was adopted to optimize the ductility and the fracture properties of the amorphous film/PI system. Tensile deformation and subsequent fracture of strained Al-Mn films on PI were investigated experimentally and by FE simulations. It was found that by sandwiching the amorphous film (20.5 at.% Mn) between two ductile copper (Cu) layers, the elongation can be improved by more than ten times, and the interfacial fracture toughness by twenty four times with a limited sacrifice of the film's fracture toughness (less than 18%). This design provides important guidelines to obtain optimized mechanical properties of future flexible electronics devices. The reliability of amorphous brittle Al-Mn (20.5 at.% Mn) thin films deposited on PI substrates is strongly influenced by the film/substrate interface adhesion. Some strategies to improve the adhesion of the interface were conducted, including roughening the surface of the PI substrate, adding a buffer layer and then tuning its thickness. Tensile testing and FE analysis of amorphous Al-Mn thin films with and without buffer layers coated on intact and plasma etched rough PI were investigated. It was found that by adding a chromium buffer layer of 75 nm on a rough PI substrate, the interface adhesion of the film/substrate can increase by almost twenty times. The obtained results would thus shed light on the interfacial engineering strategies for improving interface adhesion for flexible electronics. In the second example, a systematic investigation and characterization of the interfacial fracture toughness of the bimaterial Cu leadframe/EMC was carried out. Experiments and FE simulations were used to investigate delamination and interfacial fracture toughness of the biomaterial system. Two dimensional simulations using computational fracture mechanics tools, such as virtual crack closure technique, virtual crack extension and J-integral proved to be computationally cheap and accurate to find the interfacial fracture toughness of the bimaterial structures. The effects of temperature, moisture diffusion and mode-mixity on the interfacial fracture toughness were investigated. Testing temperature and moisture exposure significantly reduce the interfacial fracture toughness, and its relationship with the mode-mixity was achieved by fitting the results with an analytic formula.