INTRODUCTION: A substantial proportion of patients who undergo surgery for drug resistant focal epilepsy do not become seizure free. While some factors, such as the detection of hippocampal sclerosis or a resectable lesion on MRI and electroencephalogram-MRI concordance, can predict favourable outcomes in epilepsy surgery, the prognostic value of the detection of focal hypometabolism with 18F-fluorodeoxyglucose positive emission tomography (18F-FDG-PET) hypometabolism is uncertain. We propose a protocol for a systematic review and meta-analysis to examine whether localisation with 18F-FDG-PET hypometabolism predicts favourable outcomes in epilepsy surgery. METHODS AND ANALYSIS: A systematic literature search of Medline, Embase and Web of Science will be undertaken. Publications which include evaluation with 18F-FDG-PET prior to surgery for drug resistant focal epilepsy, and which report ≥12 months of postoperative surgical outcome data will be included. Non-human, non-English language publications, publications with fewer than 10 participants and unpublished data will be excluded. Screening and full-text review of publications for inclusion will be undertaken by two independent investigators, with discrepancies resolved by consensus or a third investigator. Data will be extracted and pooled using random effects meta-analysis, with heterogeneity quantified using the I2 analysis. ETHICS AND DISSEMINATION: Ethics approval is not required. Once complete, the systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022324823.