Abstract Purpose Cenobamate is approved for treating focal epilepsy and has potential for treating tumor‐related epilepsy (TRE) based on potential anti‐tumor effects, though there is little data on efficacy and safety in this patient population. Methods This was a retrospective, multi‐center study of patients with TRE who were prescribed cenobamate as adjunctive treatment between January 2020 and November 2024 at Mayo Clinic in Florida, Minnesota, and Arizona. Drug efficacy was assessed, and factors that were predictive of response to treatment were analyzed. Results A total of 17 patients were included, with 12 being drug resistant. The median seizure frequency for the entire group before starting cenobamate treatment was 12 (IQR = 4–64) per month, and after treatment at last follow‐up was 3 (IQR = 1–15) per month, with an overall 56.3% reduction. Four patients (23.5%) were seizure‐free, and 7 (41.1%) patients were responders (at least 50% seizure reduction). No adverse events were reported for patients on concurrent chemotherapy. Responders had significantly fewer seizures per month compared to non‐responders (5.72 ± 10.29 vs. 27.33 ± 30.17; p = .030). No clinical factors were predictive of responsiveness (or lack thereof) to cenobamate. Conclusions This study demonstrates that adjunctive therapy with cenobamate treatment for TRE is a feasible and potentially effective option. Clinical history, including drug resistance, did not predict drug efficacy. No adverse effects were reported in those treated with chemotherapy. Further studies are needed to validate treatment response and safety.