Despite intensive treatment regimens, around 20% of children confronted with cancer will succumb to their disease. Low survival rates of high-risk neuroblastoma and Wilms tumor patients can often be attributed to the development of therapy resistance, resulting in tumor recurrence and refractory disease. In the case of high-risk neuroblastoma and Wilms tumors, both genetic heterogeneity and epigenetic plasticity have been shown to be involved in drug resistance. Active research focuses on identifying novel treatment options that can target these emerging (epi-)genetic subpopulations, however an important challenge remains to detect these (epi-) genetic changes in time to allow a swift therapeutic intervention. In this project, I aim to integrate minimally invasive liquid biopsy assays to build a personalized monitoring strategy that can detect emerging resistance subpopulations in pediatric tumors. Next to methods already well established in the lab such as cfDNA copy number profiling, cfDNA methylation profiling and targeted sequencing of cfDNA, I will implement histone modification profiling of cfDNA using cfChIP in the toolbox. The sensitivity for the detection of low tumoral cfDNA fractions will be assessed for each assay and compared to one another by using artificial mixtures of healthy and tumoral cfDNA. Based on the sensitivity of each assay, I will build a personalized monitoring strategy for pediatric cancer patients and validate the approach in clinical samples.