Zwitterionic pharmaceuticals and personal care products can interact with adsorbents in different ways due to their various properties. In this work, the effects of hydrophobicity and electrostatic potential were explored through the adsorption of ciprofloxacin (CPX) and tetracycline (TC) onto multifunctional resins. Nonionic surface interaction was dominant for the adsorption on high-surface-area resin GMA10. Thereinto, hydrophobic and π-π interaction dominant for hydrophobic CPX and hydrophilic TC, respectively. Electrostatic interaction played an important role for high-anion-exchange-capacity resin GMA90. Upon their adsorption onto GMA50 resin, the relatively separated positive and negative electrostatic potentials of CPX+- due to the greater distance (∼12.33 Å) between the anionic and cationic groups led to electrostatic attraction and interaction (Ea = 8.64 ± 0.31 kJ/mol) and the vertical orientation of molecule on the surface. However, TC+-0 displayed nonionic surface interaction (Ea = 7.96 ± 0.14 kJ/mol) due to its relatively neutral electrostatic potential arising from the adjacent functional groups. Hence, the surface of GMA50 was covered with TC+-0 molecules adsorbed parallel to the surface, thereby restricting TC+-0 adsorption. Coexisted with monovalent salts, CPX adsorption was facilitated due to the salting-out effect. By contrast, the salting-out effect for TC was extremely weak, and TC adsorption was restrained due to the competitive adsorption of salts.