Voltammetric ion-selective electrodes (ISEs) based on poly(3-octylthiophene) (POT) in connection with ultra-thin membranes formulated with different selective receptors (i.e., ionophores) are proposed for detection of lead, copper and silver ions (Pb2+, Cu2+ and Ag+). The working mechanism of the POT-membrane electrode is based on interconnected charge transfer processes on both sides of the membrane, with the overall process depending on the electron transfer in the POT lattice ultimately linked to the ion transfer at the membrane–sample interface. This latter is demonstrated to be controlled by (i) the membrane composition and (ii) the accumulation/stripping electrochemical protocol, allowing the detection of traces of Ag+, Pb2+ and Cu2+. In the case of the Pb2+-selective electrode, the voltammogram displays several peaks that are hypothesized to correspond to different ion–ionophore stoichiometries. Following the signal related to the principal stoichiometry (1:1), a Pb2+ concentration as low as 0.1 nM is measurable. In contrast, the Cu2+- and Ag+-selective electrodes show only one peak for the corresponding ion analyte, which can be also detected at nanomolar concentrations. The results obtained with the three electrodes support their further usage for multi-ion detection in water samples through either a multi-ionophore-based electrode or multiple-electrode device. In any case, the membrane composition, in terms of the ionophore/exchanger molar ratio, is key to achieving a successful analytical application. Upcoming efforts may be directed at the replacement of traditional trace metal ion detection with the hanging mercury drop electrode to develop a more sustainable electrochemical approach without diminishing the analytical performance.