The grade control drillhole spacing and mining selectivity decisions are typically made using the resource model estimated from exploration and infill drilling data. Once production starts, large quantities of grade control data are collected to delineate ore and waste boundaries for ore control. In this work, a grade control drillhole spacing and mining selectivity optimization workflow is presented which allows the practitioner to use site specific knowledge to determine the most profitable ore control mining scenario. The densely gridded production data is used to simulate a ground truth block model from which scenarios of variable drillhole spacing and selectivity are evaluated against their corresponding costs to determine the maximum profit scenario. Eleven mining scenarios are evaluated using year production data from three distinctly heterogeneous mine with drillhole spacing and mining selectivity varying from 3 × 3 × 3 m (27 m3) to 30 × 30 × 15 m (13,500 m3). The profit differences from the optimum scenario varied by millions of dollars (1–8%) against the next best case depending on the heterogeneity of the deposit. Practitioners could apply this workflow to inform grade control drillhole spacing and mining selectivity decisions for different domains within the mine or multiple pits especially if distinctly heterogeneous volumes exist.