PURPOSE: Surgery remains the only curative option for a third of refractory epilepsy patients, though success depends on precise localization of the epileptogenic zone (EZ). This study aims to assess the clinical value of hybrid F-FDG and F-DPA-714 PET/MRI for accurate localization and precise boundary delineation. METHODS: The refractory epilepsy patients who underwent surgery at Xuanwu Hospital from November 2022 to November 2023 were retrospectively recruited. Preoperative simultaneous F-FDG and F-DPA-714 PET/MRI imaging were analyzed using the asymmetry index (AI) and a 4-point visual score, with the surgical site and pathological findings serving as the gold standard. RESULTS: A total of 43 patients (mean age: 26.30 ± 8.37 years, male: 28) were included in this study. Lesion localization accuracy within the EZ was 76.7% for F-FDG PET/MRI, 69.8% for F-DPA-714 PET/MRI, and 60.5% for conventional MRI (p = 0.26). In 26 MRI-positive cases, conventional MRI accurately localized all lesions within the EZ, with three cases showing negative findings on F-FDG images and six on F-DPA-714. Among 17 MRI-negative patients, thirteen demonstrated positive results on hybrid PET/MRI. Additionally, F-DPA-714 PET/MRI proved more effective in delineating lesion boundaries. Compared to F-FDG, the AI score was significantly lower (0.25 ± 0.18 vs. 0.46 ± 0.19, p < 0.001), while the visual score was higher (4.00 ± 2.00 vs. 3.00 ± 0.00, p = 0.01). CONCLUSION: F-DPA-714 PET/MRI can effectively complement conventional MRI in the preoperative assessment of refractory epilepsy, with localization accuracy on par with F-FDG and enhanced capability in delineating lesion boundaries.