When Max Born looked back to his life's work, he concluded: "I have restricted my work to ideal crystals though I am aware that the theory of the defects in real crystals is practically far more important. This I have left to a younger generation." Indeed, ionic point defects play an important role in determining the phase, structure, properties and functionality of oxide ceramics and thin films. In this talk, I am going to show the methodology and case studies towards a better understanding of how to tune defect chemistry to design functional oxides. I start with how we used operando X-ray diffraction and spectroscopy to probe the tuning of crystal and electronic structure of at elevated temperatures (>300°C) by controlling oxygen vacancy concentration in well-controlled model systems. I will also present some recent results on using chemical capacitance as a unique tool to accurately measure oxygen vacancy concentration and map out the phase boundary in oxide thin films. Then I am going to show the encountered complexity when we switch from well-controlled high-temperature solid/gas interfaces to less well-studied room-temperature solid/liquid interfaces. I will present our recent work on protonation of NdNiO3 to highlight the importance of room-temperature defect chemistry and our new approaches to address the challenges of investigating the defect chemistry in this new regime.