Industrial catalytic reactors are made of steel, operate at high temperatures and pressures and contain hazardous chemicals. What happens inside remains hidden. Reactor optimization requires costly trial and error or is based on simplified mathematical models employing more or less accurate transport correlations and reaction kinetics. In the present work a pilot-scale fixed-bed reactor was developed for measuring concentration and temperature profiles for n-butane oxidation to maleic anhydride on vanadyl pyrophosphate catalyst pellets under industrially-relevant conditions. The reactor was equipped with five heating zones. The reactor was modeled by particle-resolved computational fluid dynamics. The catalyst bed was created by discrete element simulation and the result was validated by comparison with experimental radial porosity profiles. Catalytic chemistry was included by a kinetic model of intrinsic reaction rates. Transport resistances and packing deviations were lumped in reaction rate multipliers determined by fitting the model to profiles measured at a uniform reactor wall temperature. Simulation results reveal strong inhomogeneities inside the bed. A hot-spot develops at uniform wall temperature. At this hot-spot temperature differences of 40 K exist on one and the same pellet with negative impact on maleic anhydride selectivity and catalyst lifetime. An optimized wall temperature profile was derived by combining knowledge from the experimental profiles at uniform wall temperature and the CFD results. A gradual increasing temperature was predicted by the model to eliminate the hot-spot and increase integral maleic anhydride selectivity at constant n-butane conversion. This prediction was confirmed by experiment. At 80% n-butane conversion the maleic anhydride selectivity could be improved by 2%. Facing the scale of the process, this improvement translates into significant n-butane savings, reduced COx emissions and increased revenue.