This study investigated the degradation of sulfolane using pressurized ozonation under varying initial concentrations and the influence of different catalysts and peroxymonosulfate activation methods on the degradation efficiency. Initial sulfolane concentrations of 1 mg L−1, 20 mg L−1, and 100 mg L−1 were tested over 120 min, revealing a degradation efficiency of 73%, 41%, and 18%, respectively. The addition of various metal ions (Zn2+, Mg2+, Cu2+, Ni2+, and Co2+) demonstrated that only zinc and magnesium enhanced degradation, with zinc achieving a 92% removal efficiency and magnesium achieving 86%. Different doses of magnesium and zinc were further tested, showing optimal degradation at specific concentrations. The combination of PMS with ozonation was explored, revealing that zinc activation did not significantly enhance degradation, while NaOH activation achieved near-total degradation, with a 100 mg L−1 NaOH concentration. Varying PMS concentrations indicated that altering pH was more effective than changing PMS dosage. Finally, the impact of pH changes in both reverse osmosis water and tap water matrices confirmed that higher pH levels significantly improved degradation efficacy, achieving up to 98% removal with NaOH concentrations of 50 mg L−1 in reverse osmosis water. These results suggest that optimizing pH and catalyst type are critical for enhancing sulfolane degradation in pressurized ozonation systems.