The role of cation promoters on the microstructure and stability of complex vanadyl pyrophosphate ((VO)2P2O7 or VPO) catalysts in the selective oxidation of n-butane to maleic anhydride (MA) is of major technological importance. Although several studies have been cited in the literature on the specific activity and MA selectivity of promoted VPO, no direct evidence for the formation of solid solutions with VPO has been reported. A better fundamental understanding of the location and the complex role of promoters in the catalyst-adsorbate interactions is therefore required. We have synthesized novel promoted catalyst powders with several cations including iron and antimony, as well as with ceria. We have probed their nanostructures in n-butane directly (in-situ) at the atomic level using environmental-HREM (EHREM) and their composition by high spatial resolution depth profiling using EDX (and STEM probe size) on the nanometer (nm) scale.