We present a case of a four-year-old male with a history of giant omphalocele who underwent ultrasound-guided Botox injection to bilateral anterior abdominal wall musculature in preparation for definitive repair. Botox administration was successfully combined with preoperative subfascial tissue expanders to achieve definitive midline closure of the anterior abdominal wall defect. Our experience suggests that Botox can be safely used as part of the treatment plan for giant omphalocele repair.