Epilepsy is the most common complication and cause of morbidity and mortality in tuberous sclerosis complex (TSC). Surgery is associated with an increased probability of achieving seizure-freedom. However, the preoperative noninvasive localisation of epileptogenic tubers remains challenging. This study aimed to identify multimodal magnetic resonance imaging (MRI) biomarkers of epilepsy in patients with TSC and develop a prediction model of epileptogenicity in these patients.Patients with TSC, with or without epilepsy, were recruited. All patients underwent MRI scanning, including T1WI, T2WI, T2W-FLAIR, DTI, and multi-parametric MR with a flexible design (MULTIPLEX). We compared the multimodal cerebral MRI characteristics of the cortical tubers, subependymal nodules, and perilesional tissue between patients with TSC with or without epilepsy and developed a prediction model for epileptogenicity.Among the patients with TSC, 32 with and 16 without epilepsy underwent MRI. Higher proton-density mapping (PD) of cortical tubers and decreased fractional anisotropy (FA), increased mean diffusivity (MD), and increased radial diffusivity (RD) of subependymal nodules were associated with epileptogenicity in both the centre and perilesional tissue, independent of TSC gene variation. Based on the above findings, we developed a prediction model for epileptogenicity with an area under the curve of 0.973, specificity of 0.909, and sensitivity of 0.963 (P < 0.001).In patients with TSC, high PD of the cortical tubers, decreased FA, and elevated MD/RD of the subependymal nodules were significantly associated with epileptogenicity. A prediction model based on multimodal cerebral MRI characteristics has the potential to evaluate the likelihood of epilepsy in patients with TSC.Copyright © 2024 Elsevier B.V. All rights reserved.