In the current electrolytic manganese industry, iron separation and reuse from iron-rich manganese ore leachate (IRMOL) has become one of the most pressing challenges. This study aimed to investigate the optimal conditions for iron separation from IRMOL and to assess the economic and practical advantages of iron separation or removal in industrial manufacturing. To identify more cost-effective and technologically advanced production circumstances, we examined five key elements that weaken Fe(OH)3 colloidal production conditions in enterprises: reaction temperature, pH, crystal species, aging, and reaction time. The screening results showed that when the conditions were optimized, the efficiency of reducing manganese loss decreased from 6.15% to 4.69%. Additionally, the generation of iron-rich electrolytic manganese residue (IREMR) was decreased by 44.32%, and the filtration velocity of IREMR increased from 0.0030 to 0.0220 mL/(s·cm2) compared to the production conditions before optimization at the enterprise. Through multiphase equilibria modeling with Visual MINTEQ, we have determined that raising the temperature and pH levels increases the expenses associated with chemicals and energy usage and results in an elevation of Fe(OH)2+ concentration. This can lead to the creation of Fe(OH)3 colloidal, causing a high water content in IREMR, inefficient filtration, and significant loss of manganese. This strategy is highly significant for the production of electrolytic manganese and the reduction of electrolytic manganese residue.