Neuroblastoma (NB), which accounts for 6-10% of all childhood tumours, is the leading cause of cancer-related deaths in children under the age of 5. This high mortality rate is due to imprecise stratification and a lack of targeted treatments. Originating from neural crest-derived (NC-derived) cells, NB results from defective differentiation caused by genomic and epigenetic impairments. NC cells, known for their multipotency and migratory nature, are frequently regarded as an embryonic model for cancer stem cells. However, the mechanisms that drive tumour initiation and progression are still largely unclear. Given that NB primarily results from a block in neuroblast differentiation, we hypothesize that understanding the molecular drivers and inhibitors, such as transcription factors (TFs), responsible for the normal transition of embryonic neuroblasts from the proliferative phase to terminally differentiated sympathetic neurons could reveal predictive markers and lead to targeted therapies for NB. Considering that this cancer shows few point mutations but demonstrates extensive variations in gene copy number and gene expression, it suggests that NB is primarily influenced by changes in RNA and protein levels rather than by mutant proteins. Furthermore, as genetic changes during embryonic development in NB affect critical genes regulated by TFs, we suggest that studying these TFs could lead to a better understanding of the major regulators of NB development. Utilizing extensive sequencing data, we have identified TFs potentially associated with NB development. Our strategy involves evaluating the expression levels of potential TFs in NB cell lines and during the in vitro differentiation of neuroblasts using human induced pluripotent stem cells (hiPSCs). We developed an in vitro neuroblast differentiation model using hiPSCs and growth factors to generate sympathetic neurons. Using gain- and loss-of-function approaches, we will assess potential regulators’ impact on differentiation, aiming to confirm key TFs as biomarkers or therapeutic targets in neuroblastoma.