As metallic multilayers exhibit large surface area-to-volume ratios, their physical and chemical properties can be size dependent. These size dependent changes facilitate both crystallographic phase transformations as well as alternations in deformation mechanisms. These topics were studied using a series of Cu based thin film architectures, where Cu was deposited between either crystalline phases, i.e. Nb or V for phase stability studies, or glassy phase, i.e. Cu45Zr55, for deformation studies. The phase stability of all the layers were monitored through real time stress measurements during the growth of the films coupled with post growth characterization methods including X-ray diffraction (XRD), transmission electron microscopy (TEM), and atom probe tomography (APT). Face centered cubic (fcc) phase transformation was detected in both multilayered systems, explained by the reduction of interfacial energy. An additional vitrification phase transformation was observed in the crystalline and Cu/Nb system owing to clusters formations at the interfaces. For the in situ deformation studies, the crystalline Cu/ amorphous Cu45Zr55 multilayers were studied by indentation and high cycle fatigue in the TEM. Precession electron diffraction (PED) quantified the grain size, grain misorientation and texture. Grain rotation, facilitated by the free surface of the TEM foil, and grain growth, were observed to be primary deformation mechanisms in the crystalline layers of the multilayers.