<p>Pesticides and DBPs coexist in tap waters at trace levels, demanding attention for long term health protection. To allocate resource for water contaminant control, regulated chemicals need to be prioritized. The current prioritization is primarily based on the toxicity additivity assumption that ranks toxicity-weighted concentration of chemicals. However, recent findings revealed that the nonadditive synergistic and antagonistic toxicological interactions are also prevalent in waters, potentially biasing previous prioritization rankings. To demonstrate a possible framework for improved prioritization, we identified the cytotoxic interactions, component contributions, and forcing compounds among six common toxic pesticides and DBPs based on the Chou-Talalay approach. In the “Malathion + DBPs” combination, the interaction type shifted from additivity to antagonism as the concentration increased, indicating concentration dependency. In the “Chlorothalonil + DBPs” combination, the strong antagonism led to a convergence of cytotoxicity value among the three mixtures. A comparison of cytotoxicity of “Deltamethrin + IAN/BAN” revealed that the interaction type affected the mixture-induced cytotoxicity. To unravel the cytotoxic interactions and forcing chemicals at both environmentally-relevant and bioaccumulation-attainable concentrations, we analyzed the componential contributions among “pesticides + DBPs” mixtures at <i>LC</i>_0.1 and <i>LC</i>₅₀ levels and identified the forcing cytotoxic compounds in each. At <i>LC</i>_0.1, pesticides need to be prioritized in only two combinations out of nine; at <i>LC</i>₅₀, DBPs should be prioritized only in “Chlorothalonil + DBPs” combinations. These results provide a framework for the prioritization among “pesticides + DBPs” in water and possibly other classes of contaminants.</p>