The study of nano‐biointeractions, at the forefront of interdisciplinary research, unveils intricate interplays between nanomaterials (NMs) and intracellular organelles, which are pivotal hubs orchestrating diverse cellular processes. Thanks also to the formation of dynamic contacts among their membranes, organelles regulate lipid exchange, calcium signaling, and metabolic pathways. Recently, the potential role of NMs in cellular homeostasis through the regulation of organelle membrane contact sites (MCSs) is emerging, and a complete overview of this issue is still lacking. This perspective aims at elucidating the synergy between functional NMs and organelle contact site research, underscoring the pivotal role of NMs in advancing the comprehension of cell biology mechanisms and fostering therapeutic breakthroughs. This subject represents a crucial aspect of nano‐biointeractions, as it can reveal new molecular targets for NMs and potentially revolutionize therapeutic strategies. Nanotechnology may offer unprecedented tools to decipher and manipulate dynamic organelle interfaces with remarkable precision. Engineered nanomaterials may serve as versatile probes and effectors, enabling targeted modulation of organelle contact sites and unraveling the molecular intricacies governing organelle dynamics. Furthermore, nano‐biointeraction‐driven insights hold promise for therapeutic innovations, offering novel avenues in diseases linked to dysregulated organelle contacts.