Objectives To evaluate the clinical value of the combination of [F-18]FDG PET/MRI and magnetoencephalography (MEG) ([F-18]FDG PET/MRI/MEG) in localizing the epileptogenic zone (EZ) in temporal lobe epilepsy (TLE) patients. Methods Seventy-three patients with localization-related TLE who underwent [F-18]FDG PET/MRI and MEG were enrolled retrospectively. PET/MRI images were interpreted by two radiologists; the focal hypometabolism on PET was identified using statistical parametric mapping (SPM). MEG spike sources were co-registered onto T1-weighted sequence and analyzed by Neuromag software. The clinical value of [F-18]FDG PET/MRI, MEG, and PET/MRI/MEG in locating the EZ was assessed using cortical resection and surgical outcomes as criteria. The correlations between surgical outcomes and modalities concordant or non-concordant with cortical resection were analyzed. Results For 46.6% (34/73) of patients, MRI showed definitely structural abnormality concordant with surgical resection. SPM results of [F-18]FDG PET showed focal temporal lobe hypometabolism concordant with surgical resection in 67.1% (49/73) of patients, while the concordant cases increased to 82.2% (60/73) patients with simultaneous MRI co-registration. MEG was concordant with surgical resection in 71.2% (52/73) of patients. The lobar localization was defined in 94.5% (69/73) of patients by the [F-18]FDG PET/MRI/MEG. The results of PET/MRI/MEG concordance with surgical resection were significantly higher than that of PET/MRI or MEG (chi(2) = 13.948, p < 0.001; chi(2) = 5.393, p = 0.020). The results of PET/MRI/MEG cortical resection concordance with surgical outcome were shown to be better than PET/MRI or MEG (chi(2) = 6.695, p = 0.012; chi(2) = 16.991, p < 0.0001). Conclusions: Presurgical evaluation by [F-18]FDG PET/MRI/MEG could improve the identification of the EZ in TLE and may further guide surgical decision-making. Key Points Lobar localization was defined in 94.5% of patients by the [F-18]FDG PET/MRI/MEG. The results of PET/MRI/MEG concordance with surgical resection were significantly higher than that of PET/MRI or MEG alone. The results of PET/MRI/MEG cortical resection concordance with surgical outcome were shown to be better than that of PET/MRI or MEG alone.