Transition metal oxide hetero-interfaces are interesting due to the distinctly different properties that can arise from their interfaces, such as memristive behavior, superconductivity, high catalytic activity and magnetism. These interfaces are the source for local heterogeneities in composition, atomic structure and electronic structure. Classically, defect redistribution is quantified at the continuum level by concurrent solution of Poisson’s equation for the electrostatic potential and the steady-state equilibrium drift-diffusion equation for each defect. It is possible to inform this level of modeling with first principles calculations of band off-sets, and defect formation and segregation energies at thermodynamically relevant conditions. This approach had numerous successful implementations, including the quantification of charge transport properties at surfaces and grain boundaries. In this talk, I will discuss three phenomena that also need to be considered in a broader framework of defect structures and distributions at oxide hetero-interfaces. 1) Presence of strong electric fields that can cause polarization of defective systems and affect the defect abundance and structure. We have assessed this effect on neutral oxygen vacancies in simple binary oxides from first principles calculations. 2) Phase change under the effect of local electrostatic potential because of a change in the electrochemical potential of oxygen. We have assessed the ability to trigger phase change electrochemically in two classes of oxides, SrCoO_x and VO_x, and have quantified the phases and the corresponding distinctly different electronic properties by combining in operando x-ray diffraction and x-ray photoelectron and absorption spectroscopy. The results have implications both for oxide hetero-interfaces and for oxide electronic devices that aim to control properties electrically. 3) Elastic strain, that affect the stability and mobility of defects. In this recent work, we have focused on the stability of electronic defects, specifically the electron polarons versus free electrons SrTiO₃, as a function of temperature and hydrostatic stress, by combining first principles calculations and quasi harmonic approximation. Our results demonstrate that it is possible to control the type of electronic defect, and so the transport properties, by means of electro-chemo-mechanics.