Background Generalized Anxiety Disorder (GAD) affects approximately 10–15% of children and adolescents. Selective Serotonin Reuptake Inhibitors (SSRIs) are among the main treatment options. Escitalopram, an SSRI for adult anxiety, is being studied for pediatric use. Predicting the treatment response could optimize interventions. This systematic review aimed to understand the safety and efficacy of escitalopram in the treatment of pediatric GAD and to determine potential treatment response indicators. Methods Searches for randomized controlled trials (RCTs) on escitalopram’s effectiveness in pediatric GAD were conducted across six databases. Two reviewers selected the trials, extracted data, and evaluated the trial quality independently. A third reviewer resolved the discrepancies. Outcomes were presented as mean differences (MDs) with 95% confidence intervals (CIs), while the Cochrane risk of bias tool was used to gauge evidence quality. Results Five RCTs including 401 patients were analyzed. Escitalopram showed a greater reduction in The Pediatric Anxiety Rating Scale PARS score than placebo (MD -6.1, 95% CI [-8.75 to -3.44] (P = 0.09, I2 = 65%)). Multiple methods have been used to predict escitalopram treatment responses, such as reaction time changes, executive functions, and Amygdala Functional Connectivity, including the CYP2C19 metabolizer phenotype. The data indicated that neuroimaging was the most effective predictor of the treatment response. Conclusion Escitalopram notably reduced PARS scores in pediatric patients with GAD. Neuroimaging, as a biomarker, is a valuable predictor of treatment response and provides insights into the neurological aspects of anxiety disorders, offering the potential for groundbreaking treatment advancements.