Permeable reactive barriers (PRBs) are being employed for in situ site remediation of groundwater that is typically flowing under natural gradients. Site characterization is of critical importance to the success of a PRB. A design-specific site exploration approach called quantitatively directed exploration (QDE) is presented. The QDE approach employs three spatially related matrices: (1) covariance of input parameters, (2) sensitivity of model outputs, and (3) covariance of model outputs to identify the most important location to explore based on a specific design. Sampling at the location that most reduces overall site uncertainty produces a higher probability of success of a particular design. The QDE approach is demonstrated on the Kansas City Plant, Kansas City, MO, a case study where a PRB was installed and failed. It is shown that additional quantitatively directed site exploration during the design phase could have prevented the remedial failure that was caused by missing a geologic body having high hydraulic conductivity at the south end of the barrier. The most contributing input parameter approach using head uncertainty clearly indicated where the next sampling should be made toward the high hydraulic conductivity zone. This case study demonstrates the need to include the specific design as well as site characterization uncertainty when choosing the sampling locations.