In comparison to conventional Pt alloys with late transition metals such as nickel and cobalt, Pt-rare earth metal alloys (Pt-RE) such as Pt-Ce, Pt-La, and Pt-Nd could have much-improved stability for the oxygen reduction reaction (ORR) in acidic media. However, this promise has only been demonstrated with polycrystalline electrodes rather than the more industrially relevant form of nanoparticles. A major challenge lies in the synthesis of Pt-RE alloy particles with well-defined shapes, sizes, and crystalline structures. We recently invented a solid-state chemical process for the synthesis of Pt-Re alloy nanoparticles. Here, we report our recent findings on the understanding of synthesis mechanisms and structural changes of Pt-RE alloy particles under operating ORR conditions, which are based on the results obtained from multiple in-situ techniques including in-situ transmission electron microscope, X-ray diffraction, and thermal-gravimetric mass spectrometry, etc. We aim to answer two questions through the studies, that is, 1) how do the alloy crystals come into formation during the synthesis? and 2) how do the structures of the alloy particles change during operating ORR conditions?