Background and Aims: Approximately 1 in 4 patients with ulcerative colitis experiences a severe exacerbation of disease requiring hospitalization, termed acute severe ulcerative colitis (ASUC). These episodes pose a major burden on patients with ulcerative colitis and early prediction of their outcomes based on clinical data is crucial to optimize therapy. Methods: A systematic review was performed using Embase and Medline for articles between 2000 and 2023. Studies obtained from the databases were uploaded on Covidence for screening by 2 independent reviewers. Quality appraisal for each study was done using the Critical Appraisals Skills Program depending on study design. Results: A total of 48 eligible studies were included in the review. The key predictors of ASUC identified in this review included clinical, endoscopic, and radiographic biomarkers, which were summarized. The main outcomes assessed in the studies were intravenous corticosteroid failure, need for rescue therapy, and need for colectomy. Score-based predictions and some novel markers were also included in the results. Conclusion: Utilization of evidence-based predictors of outcome in ASUC could serve as a powerful tool in customizing therapeutic measures and a step forward toward personalized patient care. Despite promising candidates, there remains a significant opportunity to identify and test additional clinical and laboratory-based predictors, especially early in the hospitalization and as the clinical practice and medical therapies evolve.