Neuroblastoma (NB), a rare pediatric solid tumor, accounts for 15% of childhood cancer deaths. It’s high heterogeneity, low mutational load, and strong immunosuppressive tumor microenvironment (i-TME) have hindered the success of immunotherapy. Recently, natural killer (NK) cells have stood as a promising immunotherapeutic tool, as they don’t depend on specific mutations. Still, clinical trials for NB show only modest results, proving further action is needed to overcome the iTME. Refractory tumors often respond to Ferroptosis, a novel cell death mechanism that is highly immunogenic. Cancer cells undergoing ferroptosis release HMGB1 and other recruiters of NK cells. Moreover, ferroptotic drugs can act through several mechanisms and could be adapted to different tumor characteristics. Finally, due to the high heterogeneity of NB, one-fits-all strategies are not appropriate, therefore mathematical modelling of the data obtained will help advance our ability to select personalized combinations of ferroptotic agents and NK cells based on immunogenicity and tumor characteristics. The goal of iroNKiller is to combine ferroptotic drugs with NK cell therapy to treat NB, and to perform in silico modelling of the results to predict which patients would benefit from this novel therapy.