Background: Repair of large incisional hernias remains a surgical and costly challenge. Temporary paralysis of the lateral abdominal wall muscles with topical administration of botulinum toxin A (BTA) is a new therapeutic concept, which may obviate the need for component separation technique (CST) for repair of large incisional hernias. Current literature on the administration of BTA as adjunct to surgical repair of abdominal incisional hernias was investigated. Methods: The electronic databases PubMed and Embase were searched for eligible studies. Two independent investigators evaluated the literature. Data were sought regarding primary fascial closure with and without CST, safety, hernia recurrence, method of application, and preoperative radiological imaging. Results: Six cohort studies including a total of 133 patients receiving BTA were identified. No randomized or case-control studies were found. In total, 83.5% of the patients achieved primary fascial closure. Supplemental CST was necessary in 24.1% of the patients. Two patients developed hernia recurrence during follow-up. No postoperative complications or adverse events were considered related to the administration of BTA, except for impairment of postoperative coughing and sneezing. Additionally, radiological imaging showed that BTA increased the length of lateral abdominal muscles before surgery. Conclusions: Preoperative administration of BTA increases muscle length and may facilitate primary fascial closure. Optimal administration is at least 2 weeks before repair, whereas the optimal dose of BTA remains to be defined. Carefully designed randomized controlled trials are warranted to identify patients who would benefit from BTA and to eliminate the confounding effect of CST.