Brain somatic mutations are increasingly recognized as major drivers of focal epilepsy particularly in malformations of cortical development. While traditionally relying on surgically resected tissue for genetic analysis, recent advances in molecular techniques now enable the recovery and analysis of DNA from stereo-electroencephalography (SEEG) electrodes. This minimally invasive approach provides unprecedented opportunities to identify somatic mutations in patients who may not undergo resective surgery. Here, we review the current state of molecular analyses from SEEG electrodes, including recent developments in DNA sequencing, transcriptomics, and epigenetic profiling. We discuss how genetic testing may be integrated into presurgical evaluations, providing new opportunities for comprehensive molecular phenotyping of focal epilepsies. These innovations hold promises in enhancing surgical outcome prediction and guiding toward targeted therapies.