NH2SO3H is an effective nucleation agent for the formation of atmospheric aerosols and cloud particles. So, the ammonolysis of SO3 to form NH2SO3H without and with neutral (H2O) and basic (NH3) trace gases has been extensively investigated. However, the acidic trace gas X (X = H2SO4 and CH3SO3H)-assisted ammonolysis of SO3 is still up for debate. In this work, a comprehensive theoretical investigation of X-assisted ammonolysis of SO3 and its reverse reaction (the isomerization of NH2SO3H to form SO3-···NH3+) was carried out in the gas phase and at the air-water interface. The gas-phase results show that X-assisted isomerization of NH2SO3H to form SO3-···NH3+ is more energetically and kinetically favorable than its reverse reaction and the isomerization of NH2SO3H in the presence of H2O and NH3. Such unexpected findings revealed that gas-phase NH2SO3H is highly reactive in the presence of acidic trace gas in contrast to the high stability of NH2SO3H in neutral and basic conditions. At the air-water interface, the X-assisted isomerization reaction of NH2SO3H involves multiple water molecules. The loop structure of the reaction center (X···NH2SO3H···3H2O) promotes the transfer of protons in the water molecules to form the SO3-···NH3+ ion pair, which can then interact with several interfacial water molecules to form ammonium bisulfate. These interfacial reaction channels follow a stepwise mechanism and proceed at the picosecond time-scale. The findings of this study will contribute to a better understanding of the atmospheric behavior of NH2SO3H in polluted acidic trace gases.