Conductivity enhancement of PEDOT:PSS via the morphological change of PEDOT-rich domains has been achieved by introducing a 1-ethyl-3-methylimidazolium (EMIM)-based ionic liquid (IL) into its aqueous solution, and the degree of such change varies drastically with the anion coupled to the EMIM cation constituting the IL. We carry out a series of molecular dynamics simulations on various simple model systems for the extremely complex mixtures of PEDOT:PSS and EMIM:X IL in water, varying the anion X, the IL concentration, the oligomer model of PEDOT:PSS, and the size of the model systems. The common characteristic found in all simulations is that although planar hydrophobic anions X are the most efficient for ion exchange between PEDOT:PSS and EMIM:X, they tend to bring together planar EMIM cations to PEDOT-rich domains, disrupting PEDOT π-stacks with PEDOT-X-EMIM intercalating layers. Nonplanar hydrophobic anions, which leave most of EMIM cations in water, are efficient for both ion exchange and the formation of extended PEDOT π-stacks, as observed in experiments. Based on such findings, we propose a design principle for new cations replacing EMIM; nonplanar hydrophilic cations combined with hydrophobic anions should improve IL efficiency for PEDOT:PSS treatment.