Targeted herbicide applications have the potential to reduce herbicide inputs but pose an inherent risk of missing weeds resulting in late-season escapes. Furthermore, relying on targeted residual herbicides may increase weed emergence relative to broadcast applications. Research was conducted over a three-year period in Keiser, AR, to compare traditional broadcast applications to targeted postemergence applications in glyphosate-, glufosinate-, and dicamba-resistant soybean. The herbicide program was consistent across treatments with a broadcast-applied preemergence residual, and a postemergence program including glufosinate + glyphosate + S-metolachlor followed by glufosinate + acetochlor, both broadcast- or target applied at the highest and lowest spray sensitivities. The soil seedbank was similar at trial initiation across treatments, and there was no increase over three years for broadcast and targeted applications at the highest sensitivity. Averaged over application timing, the lowest sensitivity increased the weed density from 867 plants ha-1 to 2,870 plants ha-1 in year two, to 11,300 plants ha-1 in year three. This response is likely due to more Palmer amaranth escapes at harvest (averaged over years) with >1,000 plants ha-1 compared to the highest sensitivity and broadcast treatments. Targeted applications did improve profitability by reducing herbicide use and increasing application efficiency, providing averaged savings of USD $43.22 ha-1 to $129.19 ha-1 relative to broadcast postemergence cost of $227.22 ha-1. Area sprayed was reduced by 20% to 90%, with the average at early-postemergence being 41.3% and 57.9% and at mid-postemergence equaling 48.1% and 49.3% for the lowest and highest sensitivities, respectively. The only difference in the area sprayed between sensitivity settings occurred early postemergence. Based on the results of this experiment, producers could utilize targeted applications postemergence in soybean to increase profitability, but the lowest sensitivity resulted in unacceptable increases to the weed seedbank, which could impact management in future years.