The gas-phase reactivity of XeF+ toward a model nucleophile, acetonitrile, was investigated by the joint application of experimental and theoretical methods. The results of mass spectrometric experiments and theoretical calculations up to the B3LYP/CCSD(T) level of theory show that XeF+ promotes both F+ and Xe+ transfer to CH3CN. Both processes involve the preliminary association of the reactants to yield two ion-molecule complexes, [CH3CNFXe](+) and [CH3CNXeF](+), of comparable stability. The former can undergo Xe loss, yielding CH3CNF+, which can consequently rearrange into the CH2FCNH+ isomer, more stable by 263.6 kJ mol(-1) at the CCSD(T) level of theory. The isomerization can proceed by two independent pathways and requires the overcoming of significant barriers computed to be 147.3 and 187.0 kJ mol(-1) at the same level of theory. The CH3CNF+ cation reacts with typical nucleophiles (CH3COCH3, C2H4, 1,1-C2H2F2, CH3-OH, C6H6) according to three processes, i.e., charge exchange, F+ transfer, and ion-molecule complex formation, whose relative efficiency and thermochemistry were investigated. The formation of CH3CNXe+ occurs via the loss of F from the primary ion-neutral complex [CH3CNXeF](+). The gas-phase reactivity of XeF+ is discussed in comparison with the fluorination of unsaturated molecules by XeF2 in solution.