Background: Seizures and epilepsy in multiple sclerosis (MS) have been related to grey matter (GM) pathology. However, the link between epilepsy occurrence and GM alterations in MS is still poorly understood. Hence, we aimed to investigate the integrity and network architecture of brain GM compartment in MS patients with concomitant epilepsy. Material and methods: In 30 MS patients with epilepsy (MSE; age 41 ± 15 years, 21 females), 60 MS patients without epilepsy (MS; 41 ± 12 years, 35 females), and 60 healthy subjects (HS; 40 ± 13 years, 27 females), 3T MRI was acquired and served to quantify the lesion loads, volumes of cortical, subcortical, and hippocampal structures and to reconstruct the GM networks. The topological organization of GM networks was assessed by applying the graph theoretical analysis. Results: The MSE patients compared to MS presented significantly higher lesion loads within the medial temporal cortex and hippocampal subfields (all p < 0.05). Similarly, lower volumes of temporal and parietal lobe cortices were attested in MSE patients compared to both MS and HS (all p < 0.05). On hippocampal regional level, lower volumes of hippocampal tail and presubiculum were detected in both MSE and MS patients compared to HS (all p < 0.05). Network architecture in MSE patients was characterized by a more clustered and assortative network topology compared to both MS and HS (all p < 0.05). Conclusions: High lesion load, altered integrity of mesiotemporal GM structures, and network reorganization are associated with epilepsy occurrence in MS.