Neuroblastoma is the most frequent extra-cranial solid tumor in children and accounts for 15% of childhood cancer mortality. With the currently employed intensive multi-modal therapeutic strategy, the five-year survival of high-risk patients is not better than 50%. To increase the survival rate, there is a high unmet need of targeted agents to enhance cancer-specific killing while reducing toxicity. In this context, we aim to investigate the effect of idasanutlin and dinutuximab on the different cell populations present in neuroblastoma using spatial transcriptomics, a technique capable of quantifying biomolecules while preserving their spatial context. To this purpose, tumors from two neuroblastoma mouse models and neuroblastoma patients will be analyzed using a custom sequencing-based spatial transcriptomics platform to map intra-tumoral heterogeneity during tumorigenesis and to better understand the pleiotropic treatment effects induced by these drugs. In addition, blood plasma will be collected from mice bearing neuroblastoma tumors to evaluate how well the tumor heterogeneity, as detected by spatial transcriptomics, is reflected in the blood extracellular transcriptome. We anticipate that a better understanding of molecular mechanisms of new promising treatment strategies together with a better characterization of tumor heterogeneity, will result in better or novel combination therapies to maximize patient benefit.