Background: Guidelines recommend preoperative nutrition optimization in patients with penetrating Crohn disease. However, recommendations on formulation, route of administration, and duration are lacking. The purpose of this review was to determine if a superior preoperative nutritional optimization strategy exists for patient undergoing surgery for penetrating Crohn disease. Methods: Electronic databases were searched from January 2000 to February 2021 for studies reporting preoperative nutritional optimization strategies in patients undergoing surgery for septic complications from penetrating Crohn disease. Information pertaining to study design, patient population, preoperative nutritional optimization strategy, and postoperative adverse events were extracted. Qualitative synthesis and meta-analysis using a random-effects model were performed as appropriate. Results: Seven retrospective, 5 prospective cohort, and 1 randomized controlled trial involving 1518 patients were included. Seven studies compared exclusive enteral nutrition (EEN) to standard of care; the remainder compared various other nutritional regimens, including oral nutritional supplementation and parenteral nutrition. In the meta-analysis of studies comparing EEN to standard of care, EEN was associated with reduction in anastomotic leak (odds ratio OR 0.41, 95% confidence interval CI 0.20-0.84, n = 5 studies, 587 patients), wound infection (OR 0.47, 95% CI 0.3-0.75, n = 6 studies, 657 patients), and a trend toward reduction in postoperative adverse events (OR 0.56, 95% CI 0.31-1.01). There was no difference in risk of diverting loop ileostomy at the time of surgery or length of hospital stay. This review had several limitations. First, the majority of included studies were retrospective and observational in nature; this likely introduced significant selection bias into the results, thereby limiting the certainty of conclusions that can be drawn from this meta-analysis. Furthermore, the limited number of studies reporting adjusted data precluded sensitivity analysis of adjusted data. There was also appreciable heterogeneity in baseline characteristics of included patient populations as well as in the formulation and duration of the prescribed nutritional regimens. Finally, the lack of studies evaluating nutritional optimization strategies other than EEN, such as parenteral nutrition, limits our ability to determine and compare the efficacy of these techniques. Conclusion: Nutritional optimization with EEN may be associated with improved postoperative outcomes in patients undergoing bowel resection for penetrating Crohn disease, specifically anastomotic leak and wound infection. The development of a standardized evidence-based preoperative nutritional optimization strategy is warranted for this complex patient population.