Background: Allergen immunotherapy (AIT)-associated adverse events are a major concern for the safety and efficacy of AIT. Omalizumab is a novel anti-IgE monoclonal antibody for the treatment of allergic diseases. At present, there is no agreement on whether combining omalizumab with AIT could improve such conditions. Objective: To identify the superiority of combining omalizumab and AIT in allergic diseases. Methods: A thorough search of the Pubmed, MEDLINE, and Cochrane Library databases was conducted to find randomized controlled trials reporting the combination of omalizumab in AIT. A fixed-effects model was used to estimate the safety and efficacy with 95% confidence interval. Results: The inclusion criteria for the meta-analysis were met by a total of 10 randomized controlled studies (containing 871 patients). According to a pooled analysis, individuals receiving omalizumab reported significantly fewer episodes of severe systemic adverse reaction compared to control patients (RR 0.36, 95% CI 0.22 to 0.58). Similarly, the addition of omalizumab significantly increased the number of patients achieving target maintenance dose (TMD) and sustained unresponsiveness to allergen (SU) (RR 1.33, 95% CI 1.16 to 1.48; and RR 2.55, 95%CI 1.56 to 4.17, respectively) than the control group. Meanwhile, the improvement in symptom severity score (MD -0.28, 95%CI -0.31 to -0.25), rescue medicine daily means score (MD -0.12, 95%CI -0.22 to -0.09), and the number of patients consuming epinephrine in AIT(RR 0.30, 95%CI 0.15 to 0.63)were also displayed superior to control. Conclusion: Omalizumab can significantly enhance the safety and efficacy of AIT by decreasing the frequency of severe systemic adverse events and increasing TMD.