We report and study the translation of the high catalytic oxygen electroreduction activities of nanostructured Molybdenum-doped octahedrally-shaped PtNiMo particles from conventional thin-film rotating disk electrode screenings (3.43 ± 0.35 A mgPt-1 at 0.9 VRHE) to Membrane Electrode Assembly (MEA)-based single fuel cell tests with sustained Pt mass activities of 0.45 A mgPt-1 at 0.9 Vcell, one of the highest ever reported performances for advanced shaped Pt alloys in real devices. Scanning transmission electron microscopy with energy dispersive X-ray analysis (STEM-EDX) evidences that Mo preferentially occupies the Pt rich edges and vertices of the element-anisotropic octahedral PtNi particles. Furthermore, combining in situ wide angle X-ray spectroscopy, X-ray fluorescence and STEM-EDX elemental mapping with electrochemical measurements we finally succeeded to realize high Ni retention in activated PtNiMo nanoparticles even after prolonged potential-cycling stability tests. Stability losses at the anodic potential limits were mainly attributed to the loss of octahedral particle shape. Extending the anodic potential limits of the tests to the Pt oxidation region induced detectable Ni losses and structural changes. Our study shows on an atomic level how Mo adatoms on the surface impact the Ni surface composition which, in turn, gives rise to the exceptionally high experimental catalytic ORR reactivity and calls for strategies on how to preserve this particular surface composition to arrive at performance stabilities comparable with state-of-the-art spherical dealloyed Pt core shell catalysts.