Solid oxide fuel cells (SOFCs) have attracted significant attention over recent years due to their promising use as source of clean and efficient power generation. Towards the goal of enhancing the efficiency of these devices, it is important to eludicate the mechanisms governing fundamental electrochemical processes, specifically oxygen surface exchange reactions occurring at the solid cathode surface, and incorporation and transport of oxygen species across heterostructures. Among the available techniques for evaluating oxygen diffusion in mixed ionic–electronic conducting materials, isotopic exchange in conjunction with secondary ion mass spectroscopy (SIMS) depth profile analysis is one of the most extensively used and is capable of providing high-quality results. This technique consists of exposing a material to ¹⁸O isotopic tracer at a specified temperature and duration, and its concentration profile as a function of depth into the material is then evaluated through SIMS depth profile analysis. Consequently the oxygen surface exchange coefficient (k*) and the ionic diffusion coefficient (D*) can be extracted from a fitting of the ¹⁸O concentration which relates these two parameters through an appropriate solution of Fick’s Law. Using this well-established technique, we examined several relevant fluorite and perovskite oxides commonly utilized as component materials for intermediate-temperature SOFCs, including LSC (LaSrCoO₃) and LSCF (LaSrCoFeO₃) for cathodes, and GDC (gadolinia-doped ceria) for interlayers in conjunction with yttria-stabilized zirconia (YSZ) electrolytes. To examine the oxygen surface exchange kinetics in these materials, a simplified approach usually consists of fabricating these into dense, thin films by means of epitaxial deposition methods such as pulsed laser deposition (PLD). Adopting this approach, we investigated the effect of film microstructure and crystalline orientation on oxygen surface exchange kinetics and transport across various heterostructures of PLD-grown LSC, LSCF, and GDC thin films of various thicknesses prepared on (100) and (111) YSZ single crystal substrates. We found that nanograined thin films consistently exhibited higher ¹⁸O concentration as compared to quasi-single-crystalline thin films, indicating enhancement of oxygen reactivity facilitated via highly dense grain boundaries. Moreover, LSC and LSCF thin films having (100)-pseudocubic orientation exhibited more enhanced oxygen surface exchange kinetics compared to (110)-oriented films, suggesting that the type of surface termination highly influences surface reactivity. Furthermore, as degradation of cell performance has been attributed to the formation of SrZrO₃ (SZ) resulting from cation interdiffusion across LSCF/GDC/YSZ, we also examined in detail the effect of this phase on oxide ion transport in multilayered heterostructures. Oxide ion transport appears to be drastically inhibited at the SZ/YSZ interface, indicating the existence of an oxide ion barrier which blocks ionic flow. These results demonstrate the versatility of the technique to further our understanding of oxide ion transport occurring across various heterostructures and heterointerfaces, which hopefully would lead towards envisaging new structures and interfaces for high-performance SOFCs.