During the early stages of mining operations, a copper-cobalt processing enterprise in the Democratic Republic of Congo (DRC) accumulated a large quantity of oxidized ore characterized by high acid consumption and a high degree of oxidation. If subjected to direct leaching with the existing processing method, the acid consumption could reach up to 300 kg/t, significantly reducing the process’s economic viability. To address this issue, the company constructed a flotation system to treat this particular type of ore. However, previous studies indicated that the flotation of this oxidized copper-cobalt ore exhibited low recovery rates (with copper recovery at only 80% according to design) and excessive reagent consumption. Consequently, optimizing the current process to improve the flotation indices and providing technical support for the system’s industrial commissioning became urgent. In this research, a comprehensive process mineralogical study of the oxidized copper-cobalt ore was conducted. It was identified that slime coating and excess dolomite were the main factors limiting flotation recovery. Based on these findings and in accordance with ore characteristics, the study investigated applying a “fine particle rapid flotation” technique to improve flotation indices. Furthermore, a combined regulator composed of sodium citrate and sodium hydrosulfide was developed by exploring highly effective modifying agents. By integrating this reagent scheme with the “fine particle rapid flotation” technology, the process achieved favorable beneficiation indices: copper recovery of 85.64%, cobalt recovery of 86.61%, and acid consumption of 6,606 kg per ton of copper produced. Accordingly, a practical process route was proposed as a technological reference for optimizing flotation indices of similar ore deposits in the DRC.