Radiation-generated secondary electrons can induce resonance processes in a target molecule and fragment it via different pathways. Although the associating electronic resonant states at equilibrium geometry have been well studied for many target molecules in the gas phase, vibrational resonance contributions and the solvent effect are still poorly understood for relevant processes in solution. Taking a radiosensitive drug, 5-bromopyrimidine (5-BrPy), as an example, we here present a combined ab initio molecular dynamics simulation and time-dependent wave packet study with an emphasis on vibrational resonance and solvation effects on excess electron interaction with 5-BrPy in solution. The gaseous results reveal two primary channels for the electron induced C–Br bond cleavage: the highest vibrational resonance on vertical potential energy curve via a tunneling mechanism , and auto-dissociation along repulsive relaxed potential energy curve , which account for the two peaks at 0.2 and 0 eV observed in Modelli's experiment. However, a strong solvation effect modifies the mechanism and dynamics of the dissociation of the electron⋯5-BrPy system. On one hand, the spontaneous dissociation becomes unfavorable due to a barrier on the relaxed free energy surface created by the coupling between the π* and σ* states. Seven vibrational resonances (v = 0–6) are identified for the solution process and only the high-level v = 5, 6 with non-negligible quantum tunneling coefficient can cause the dissociation . On the other hand, protonation is also observed at the N sites of the hydrated 5-BrPy anion , and this inhibits the dissociation along the C–Br bond, suggesting a competing pathway against C–Br bond cleavage. Clearly, this work provides a combination strategy using an ab initio molecular dynamics technique and time-dependent wave packet method to explore the effects of vibrational resonances and solvation on the interaction of radio-generated excess electrons with target biological molecules in complicated solution surroundings.