This Article describes findings of the correlation between the atomic scale structure and the electrocatalytic performance of nanoengineered PtNiFe/C catalysts treated at different temperatures for oxygen reduction reaction, aiming at providing a new fundamental insight into the role of the detailed atomic alloying and interaction structures of the catalysts in fuel cell reactions. Both mass and specific activities of the catalysts were determined using rotating disk electrode and proton exchange membrane fuel cell. The mass activities extracted from the kinetic regions in both measurements revealed a consistent trend of decreasing activity with increasing temperature. However, the specific activity data from RDE revealed an opposite trend, that is, increasing activity with increasing temperature. In addition to TEM, XRD, and XPS characterizations, a detailed XAFS analysis of the atomic scale coordination structures was carried out, revealing increased heteroatomic coordination with improved alloying structures for the catalyst treated at the elevated temperatures. XPS analysis has further revealed a reduced surface concentration of Pt for the catalyst for the high temperature treated catalyst. The higher mass activity for the lower temperature treated catalyst is due to Pt surface enrichment on the surface sites, whereas the higher specific activity for the higher temperature treated catalyst reflects an enhanced Pt-alloying surface sites. These findings have thus provided a new insight for assessing the structural correlation of the electrocatalytic activity with the fcc-type lattice change and the atomic scale alloying characteristics. Implications of these findings to the design of highly active alloy electrocatalysts are discussed, along with their enhanced electrocatalytic performance in the fuel cell.