Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive degeneration of midbrain dopamine neurons. Current treatments mainly rely on pharmacotherapy, which seems to provide beneficial effects only in the very early stages of the disease. Having an in vitro source of mature midbrain dopamine neurons from patients is paramount to initially reproduce disease phenotypes and subsequently identify disease-modifying drug candidates. In this context, three-dimensional (3D) induced pluripotent stem cell (iPSC)-derived brain organoids play an important role, as they mimic both cell-cell interactions and cytoarchitecture of the in vivo environment and can sustain longer-term maturation than what can be achieved with 2D adherent cultures.Here we show the formation of a complex 3D in vitro model, called combinoids. These 3D units allowed us to improve the generation of ventral midbrain dopamine (VmDA) neurons, in comparison to the current midbrain culture systems, by co-culturing the VmDA neurons with their proper cell targets. In addition, the combinoids showed long-term survival, integration, and expression of key markers after transplantation in a PD animal model. Our results show successful derivation and long-term survival of combinoids, both in vitro and in vivo, and we are currently evaluating their functionality.In conclusion, these units represent an invaluable tool for disease modeling, particularly in the PD context, and could be used for developmental studies as well as future high-throughput drug discovery.