Poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TFE) is confined between alternating layers of poly(ethylene terephthalate) (PET) utilizing a unique multilayer processing technology, in which PVDF-TFE and PET are melt-processed in a continuous fashion. Postprocessing techniques including biaxial orientation and melt recrystallization were used to tune the crystal orientation of the PVDF-TFE layers, as well as achieve crystallinity in the PET layers through strain-induced crystallization and thermal annealing during the melt recrystallization step. A volume additive model was used to extract the effect of crystal orientation within the PVDF-TFE layers and revealed a significant enhancement in the modulus from 730 MPa in the as-extruded state (isotropic) to 840 MPa in the biaxially oriented state (on-edge) to 2230 MPa in the melt-recrystallized state (in-plane). Subsequently, in situ wide-angle X-ray scattering was used to observe the crystal structure evolution during uniaxial deformation in both the as-extruded and melt-recrystallized states. It is observed that the low-temperature ferroelectric PVDF-TFE crystal phase in the as-extruded state exhibits equatorial sharpening of the 110 and 200 crystal peaks during deformation, quantified using the Hermans orientation function, while in the melt-recrystallized state, an overall increase in the crystallinity occurs during deformation. Thus, we correlated the mechanical response (strain hardening) of the films to these respective evolved crystal structures and highlighted the ability to tailor mechanical response. With a better understanding of the structural evolution during deformation, it is possible to more fully characterize the structural response to handling during use of the high-barrier PVDF-TFE/PET multilayer films as commercial dielectrics and packaging materials.