Background: Circulating tumor DNA (ctDNA) is an effective and noninvasive supplementary approach for assessing minimum tumor burden in a range of solid tumors; however, studies on pediatric soft tissue sarcoma (STS) are limited. The purpose of the study was to assess the utility of ctDNA detection in predicting patient response and recurrence, and to inform treatment strategies through dynamic monitoring of ctDNA during the treatment of various types of pediatric STS. Methods: From January 2022 to January 2023, a total of 27 tissues and 112 plasma samples were obtained at baseline and during treatment. Utilizing the next-generation sequencing approach, ctDNA profiling was performed on tissue and plasma samples from 48 pediatric STS ( < 18 years old) with a panel of 481 sarcoma-specific genes (Nanjing Geneseeq Technology Inc.). Results: The study included thirty patients with rhabdomyosarcoma, nine Ewing sarcoma, and nine other subtypes of sarcoma, with 52.1% (n = 25) female. Seven patients were stages I-II, and 24 were stages III-IV. At baseline, ctDNA was identified in 56.25 % (18/32) of plasma before chemotherapy and 87.50 % (14/16) of plasma before surgery. Comparable mutational burdens were seen in baseline tissue and plasma samples, with an average of 3.8 and 3 mutations per sample, respectively. The concordance of detected mutations between tissue and plasma was 64.3%. The average plasma abundance (p = 0.007), maximum abundance (p = 0.0045), ctDNA concentration (hGE/ml) (p = 0.0005), and relative ctDNA abundance (p = 0.0083) of stage IV patients (n = 5) were higher than those of stage I-III patients (n = 6). Following surgical resection, four patients (25 %, 4/16) had detectable ctDNA. In the longitudinal monitoring, we found a high correlation (75.86 %, 22/29) between ctDNA trend and clinical response. Notably, ctDNA positive in Ewing sarcoma had the strongest correlation with clinical response. The inconsistency between ctDNA detection and clinical response could be attributed to the presence of bone lesions (57.1%, 4/7). One patient was observed to have positive ctDNA before any radiological findings. Conclusions: Our findings showed that it is feasible to use ctDNA to dynamically monitor tumor burden in pediatric soft tissue sarcoma, especially Ewing sarcoma. ctDNA may serve as a safe, non-invasive option complementary to imaging assessment of sarcoma, and further clinical benefits are being investigated.