• Synergistic activation with Cu2+ and Pb2+ significantly enhances hemimorphite flotation recovery compared to individual activation.
• The combined activation forms a more robust adsorption layer on the mineral surface, increasing active product content and xanthate adsorption.
• This innovative scheme improves surface hydrophobicity and reactivity, offering a promising approach for beneficiating refractory zinc oxide ores.
• The study provides mechanistic insights into the synergistic effects of metal ions on hemimorphite flotation, guiding future reagent design.