Magnetic resonance imaging (MRI)-negative epilepsy may be successfully solved with a multidisciplinary approach using invasive recordings, image and signal analysis. The whole methodology used by the epilepsy surgery team is systematically described based on an resistant epilepsy case with all steps and rationale of choosing different investigation methods from surface electroencephalography (EEG) to invasive recordings. Due to negative MRI and non-concordant ictal surface EEG with clinical semiology, the patient was investigated with stereo- EEG (SEEG), aiming to delimitate epileptogenic and eloquent cerebral areas. Implantation strategy, seizures recordings, stimulation, resection planning using quantitative EEG analysis, and the surgery plan are presented. The patient has been seizure-free for 14 months so far, with improved behavior and daily life quality. Post-operative examination revealed focal cortical dysplasia type II B.