Thermoelectric energy-conversion technology based on oxide materials offers promising advantages over “traditional” non-oxide and intermetallics systems due to higher stability of oxides at elevated temperatures and in various redox conditions, high natural abundance and favourable environmental issues. Oxides also possess a unique defect chemistry, which can be precisely controlled by external redox conditions and redox-sensitive substitutions. Donor-substituted strontium titanate SrTiO3 represents a family of promising n-type thermoelectric materials, with specific electronic structure tunable via introduction of structural defects, and prevailing lattice contribution to the thermal transport, enabling various lattice engineering approaches to suppress the thermal conductivity. Based on review of the recently published research results, this chapter aims to demonstrate how, through controlled defect chemistry engineering in SrTiO3-based materials, one can tune the thermoelectric performance, breaking the coupling between thermal and electrical properties. The approach is based on compositional design in model systems, where prevailing defect types are shifted from extended oxygen-rich planes to oxygen vacancies, accompanied by presence of the A-site cationic deficiency. The contributions from various defects in the crystal lattice into electronic and thermal transport are demonstrated and discussed. The concept represents particular interest for thermoelectric films and superlattices based on strontium titanate, where introduction of specific defect types with potential impact on thermoelectric performance can be achieved in easier and/or more controllable manner.