Resolution V of the 2^10-3 fractional factorial design method was used to identify the main effects and second-order interaction effects of pollutants (copper, cadmium, lead, zinc, nickel, dimethoate, metalaxyl, atrazine, malathion, and prometryn) on metals adsorption onto sediments, and 2D-QSAR models were established to reveal the relationships between metal ion characteristics and the effects of pollutants on metals adsorption. The effects on Cd adsorption were attributed to the main effects of pollutant factor concentrations, while the effects on Cu, Pb, Zn, and Ni adsorption were from the second-order interaction effect. No interference with Cd adsorption was observed, and the synergistic contribution of the main effects and second-order interaction effects on Ni adsorption was 67.26%. Additionally, the antagonistic contribution rates to Cu, Zn, and Pb adsorption reached 55.31%, 73.16%, and 86.23%, respectively. Significant correlations existed between the main effects and ionization potential (IP), the change in ionization potential (ΔIP) and ion hydrolysis ability of metals, and the second-order interaction effects with atomic number, atomic weight, and polarizing power (Z²/r) of metals. The electrochemical potential, ΔIP and IP of metals were found to promote adsorption, Z²/r, electronegativity and atomic radius of metals to inhibit adsorption significantly. Overall, the results provide theoretical support that helps elucidate compound pollution regulation among heavy metal pollutants in complex environmental systems.