This meta-analysis evaluated the efficacy and safety of nemolizumab in treating prurigo nodularis through a systematic review of randomized controlled trials. A comprehensive literature search was conducted across multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science, identifying relevant studies until January 5th 2025. Four randomized controlled trials involving 859 participants were included in the final analysis. The primary outcomes assessed were itching response measured by the Worst Itch Numeric Rating Scale (WI-NRS) and Investigator's Global Assessment (IGA) success. Nemolizumab demonstrated significant improvement in itch response compared to control, with a risk ratio of 3.52 (95% CI: 2.48 to 5.02, p <
0.00001) and low heterogeneity (I² = 28%). Similarly, IGA success rates were notably higher in the nemolizumab group, with a risk ratio of 4.40 (95% CI: 2.86 to 6.75, p <
0.00001) and low heterogeneity (I² = 11%). While adverse events were slightly more frequent in the nemolizumab group, the difference was not statistically significant (RR: 1.11, 95% CI: 0.99 to 1.24). The analysis was limited by the small number of included trials, relatively short follow-up periods, and lack of subgroup analysis. Despite these limitations, the findings suggest that nemolizumab is an effective and well-tolerated treatment for prurigo nodularis. Further research with longer follow-up periods and larger, more diverse patient populations is recommended to establish the long-term efficacy and safety profile of nemolizumab in treating this condition.