Abstract This study presents a novel approach to improve the performance of microelectrode arrays (MEAs) used for electrophysiological studies of neuronal networks. The integration of 3D nanowires (NWs) with MEAs increases the surface‐to‐volume ratio, which enables subcellular interactions and high‐resolution neuronal signal recording. However, these devices suffer from high initial interface impedance and limited charge transfer capacity due to their small effective area. To overcome these limitations, the integration of conductive polymer coatings, poly(3,4‐ethylenedioxythiophene)‐poly(styrenesulfonate) (PEDOT:PSS) is investigated as a mean of improving the charge transfer capacity and biocompatibility of MEAs. The study combines platinum silicide‐based metallic 3D nanowires electrodes with electrodeposited PEDOT:PSS coatings to deposit ultra‐thin (<50 nm) layers of conductive polymer onto metallic electrodes with very high selectivity. The polymer‐coated electrodes were fully characterized electrochemically and morphologically to establish a direct relationship between synthesis conditions, morphology, and conductive features. Results show that PEDOT‐coated electrodes exhibit thickness‐dependent improved stimulation and recording performances, offering new perspectives for neuronal interfacing with optimal cell engulfment to enable the study of neuronal activity with acute spatial and signal resolution at the sub‐cellular level.