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The detection limit of ion-selective electrodes (ISEs) is of great interest because of the many possible practical applications of ISEs in trace analysis. Existing theoretical interpretations of the detection limit of ISEs are restricted by severe assumptions such as steady-state and electroneutrality, which hamper theorizing on this problem. For this reason, the Nernst-Planck-Poisson (NPP) equations are used to predict and visualize the detection limit variability under nonequilibrium conditions. For the first time, the NPP model is applied to the so-called inverse problem: finding the optimal measurement time and inner solution concentration for lowering the detection limit.