Crosshole resistivity tomography has received consideration as a tool for quantitative imaging of carbon dioxide stored in deep saline aquifers. With regard to the monitoring responsibility of site operators and the substantial expenses associated with permanent downhole installations, optimized experimental design gains particular importance. Based on an iterative appraisal of the formal model resolution matrix, we developed a method to estimate optimum electrode locations along the borehole trajectories with the objective to maximize the imaging capability within a prescribed target horizon. For the presented crosshole case, these layouts were found to be symmetric, exhibiting refined electrode spacings within the target horizon. Our results revealed that a sparse but well conceived set of electrodes can provide a large part of the information content offered by comparably dense electrode distributions. In addition, the optimized layout outperformed equidistant setups with the same number of electrodes because its resolution was focused on the monitoring target. The optimized electrode layouts presented provided a powerful and cost-efficient opportunity to complement permanent installations, particularly at, but not limited to, future storage sites. Although preliminarily developed to support the design of crosshole resistivity layouts, our approach is directly applicable to other survey geometries including surface and surface-to-hole acquisitions.