Objective To report clinical experience with presurgical evaluation in patients with insulo-opercular epilepsy. Quantitative analysis on PET imaging and stereoelectroencephalography (SEEG) signals was used to summarize their electroclinical features. Methods Twenty-two patients with focal epilepsy arising from the insular and/or opercular cortex according to SEEG were retrospectively analyzed. Presurgical noninvasive data were analyzed in detail. Interictal PET data of patients were then statistically compared with those of healthy controls to identify the interictal hypometabolic network. The epileptogenicity index (EI) of ictal SEEG signal was computed to identify areas of spread at the beginning of seizure onset. Results Focal tonic seizures of the face and/or neck (16/22, 73%) were the most prevalent early objective signs. Epileptic discharges in the interictal and ictal scalp-EEG mostly showed an ipsilateral perisylvian distribution. Statistical analysis of interictal PET showed significant hypometabolism in the insular lobe, central operculum, supplementary motor area, middle cingulate cortex, bilateral caudate nuclei, and putamen. According to the EI analysis, insulo-opercular epilepsy could be classified as insulo-opercular epilepsy (50%), opercular epilepsy (41%), and insular cortex epilepsy (9%). Significance Clinical diagnosis of insulo-opercular epilepsy is challenging because of its complex seizure semiology and nonlocalizing discharges on scalp-EEG. A common hypometabolic network involving the insulo-opercular cortex, mesial frontal cortex and subcortical nuclei may be involved in the organization of the insulo-opercular epilepsy network. Furthermore, quantified SEEG analysis suggested that pure insular epilepsy is rare, and the close connection between insular and opercular cortex necessitates SEEG implantation to define the epileptogenic zone.