To explore the role of the interictal and ictal SPECT to identity functional neuroimaging biomarkers for SUDEP risk stratification in patients with drug-resistant focal epilepsy (DRFE). Twenty-nine interictal-ictal Single photon emission computed tomography (SPECT) scans were obtained from nine DRFE patients. A methodology for the relative quantification of cerebral blood flow of 74 cortical and sub-cortical structures was employed. The optimal number of clusters (K) was estimated using a modified v-fold cross-validation for the use of K means algorithm. The two regions of interest (ROIs) that represent the hypoperfused and hyperperfused areas were identified. To select the structures related to the SUDEP-7 inventory score, a data mining method that computes an automatic feature selection was used. During the interictal and ictal state, the hyperperfused ROIs in the largest part of patients were the bilateral rectus gyrus, putamen as well as globus pallidus ipsilateral to the seizure onset zone. The hypoperfused ROIs included the red nucleus, substantia nigra, medulla, and entorhinal area. The findings indicated that the nearly invariability in the perfusion pattern during the interictal to ictal transition observed in the ipsi-lateral putamen F = 12.60, p = 0.03, entorhinal area F = 25.80, p = 0.01, and temporal middle gyrus F = 12.60, p = 0.03 is a potential biomarker of SUDEP risk. The results presented in this paper allowed identifying hypo- and hyperperfused brain regions during the ictal and interictal state potentially related to SUDEP risk stratification.