We present the preparation of nanostructured conducting PEDOT:PSS thin films by solvent vapor annealing (SVA), using the low boiling point solvent tetrahydrofuran (THF). An Atomic Force Microscopy (AFM) study allowed the observation of distinct nanostructure development as a function of solvent exposure time. Moreover, the nanostructures’ physical properties were evaluated by nanomechanical, nanoelectrical, and nano-FTIR measurements. In this way, we were able to differentiate the local response of the developed phases and to identify their chemical nature. The combination of these techniques allowed to demonstrate that exposure to THF is a facile method to effectively and selectively modify the surface nanostructure of PEDOT:PSS, and thereafter its final properties. Moreover, our nanoscale studies provided evidence about the molecular rearrangements that PEDOT:PSS suffers during nanostructure fabrication, a fundamental fact in order to expand the potential applications of this polymer in thermoelectric and optoelectronic devices.