Functionalized nanowire arrays as cell culture substrates build a promising platform for drug delivery, stimulation, and biosensing in interdisciplinary research fields such as medicine and bioengineering. The geometrical characteristics of the nanowire array majorly influence the interaction between cell and substrate and effectively determine the range of feasible applications. But likewise, such challenging geometries potentially influence the cell’s behavior beyond the intended purpose. In this contribution, we explore the behavior of human induced neuronal progenitor cells (NPCs) and human iPSC-derived neurons when cultured on nanowire arrays with altered geometric characteristics. We demonstrate that NPCs maintain their ability to proliferate for a wide range of nanowire lengths and array pitches despite heavy deformation of the cell membrane and the nucleus. Surprisingly, for long nanowires combined with a small array pitch—resulting in a fakir-like state—we observe a significantly decreased proliferation presumably caused by prevalent stress in the cytoskeleton. For the differentiation into neurons, we show that the typically delicate culturing protocols are robust enough to overcome the impact of the substrate topology. As a result, equivalently electrophysiologically mature dopaminergic and glutamatergic neurons are generated compared to planar control samples. As a consequence, patient-derived neurons designed for neurodegenerative disease studies could be applied to functionalized nanowire arrays opening the arena for next-generation of disease studies in near future.