Simple SummaryNeuroblastoma is a pediatric tumor originating from the precursors of sympathetic nerves. The disease is known for its high heterogeneity. Hence, developing adequate preclinical models reflecting the complex biology of neuroblastoma is particularly challenging. This paper describes the current status of the available neuroblastoma models with their strengths and limitations, and demonstrates the future perspectives for preclinical neuroblastoma research.AbstractPreclinical in vitro and in vivo models remain indispensable tools in cancer research. These classic models, including two- and three-dimensional cell culture techniques and animal models, are crucial for basic and translational studies. However, each model has its own limitations and typically does not fully recapitulate the course of the human disease. Therefore, there is an urgent need for the development of novel, advanced systems that can allow for efficient evaluation of the mechanisms underlying cancer development and progression, more accurately reflect the disease pathophysiology and complexity, and effectively inform therapeutic decisions for patients. Preclinical models are especially important for rare cancers, such as neuroblastoma, where the availability of patient-derived specimens that could be used for potential therapy evaluation and screening is limited. Neuroblastoma modeling is further complicated by the disease heterogeneity. In this review, we present the current status of preclinical models for neuroblastoma research, discuss their development and characteristics emphasizing strengths and limitations, and describe the necessity of the development of novel, more advanced and clinically relevant approaches.