Thermo-mechanical processing of uranium-10 wt% molybdenum (U-10Mo) alloy fuel plates with a zirconium (Zr) interlayer leads to microstructure changes at fuel/interlayer interfaces. Secondary phases formed at this interface are particularly important to interfacial bond strength, process optimization, and maintaining structural integrity of the fuel plates during irradiation. In this work, we determined the phases and phase transformation products occurring at the interface of the U-10Mo fuel and Zr interlayer when fuel plates are subjected to short and long hot isostatic pressing (HIP) cycles. Interfacial morphology, crystal structure and composition of phases formed, and relative hardness across the U-10Mo/Zr interfaces were studied using a multi-length scale, multi-modal characterization approach involving electron microscopy, atom probe tomography, and atomic force microscopy. Results highlight that the extent of phase transformations, secondary phase formation, and hardness variability across interfaces can be controlled by modifying processing parameters. In addition, phases formed at U-10Mo/Zr interfaces are similar for both HIP process conditions, however, phase distribution, interface thickness, and relative hardness vary significantly. The extent of the discontinuous precipitation reaction leading to α-U formation is also impacted by temperature and pressure in the HIP step; greater time at elevated temperature/pressure increases extent of the DP reaction.