Background: Vascular anomalies are rare congenital disorders associated with significant morbidity. Local therapies may be insufficient for complex lesions. Sirolimus, an mTOR inhibitor, is a promising systemic treatment option. Methods: We retrospectively analyzed pediatric patients with vascular anomalies treated with sirolimus between October 2020 and June 2025. Of 29 patients who initiated treatment, 23 completed at least 12 months of therapy and had evaluable 12-month outcomes; these patients constituted the primary 12-month efficacy cohort. Treatment discontinuations were analyzed separately, and an all-treated sensitivity analysis was performed. Results: The cohort included 10 patients (43%) with lymphatic malformations (LMs), 9 (39%) with venous malformations (VMs), 2 (9%) with combined malformations, and 2 (9%) with other vascular anomalies. At 12 months, magnetic resonance imaging (MRI) demonstrated lesion size reduction in 17/23 patients (74%), stabilization in 5/23 (22%), and progression in 1/23 patients (4%). In a conservative sensitivity analysis including all 29 treated patients and classifying patients without an evaluable 12-month outcome, documented reduction or stabilization was observed in 22/29 patients (76%). Additional treatment was less frequent during treatment (30% vs. 65%, p = 0.043), although observation periods differed. Pain decreased (p = 0.021), and physical activity increased (p = 0.034). No severe adverse events led to permanent treatment discontinuation. The most common adverse events were laboratory abnormalities (47%) and aphthous stomatitis (32%). Exploratory Multiple Factor Analysis (MFA) demonstrated substantial multidimensional heterogeneity but did not identify stable radiological response phenotypes. Conclusions: Sirolimus was associated with radiological improvement or stabilization, symptom relief, and fewer additional interventions in pediatric vascular anomalies, with generally favorable tolerability.