The synthesis and optimization of polymeric inclusion membranes (PIMs) for the transport of Cd(II) and Pb(II) and their separation from Zn(II) in aqueous saline media are presented. The effects of NaCl concentrations, pH, matrix nature, and metal ion concentrations in the feed phase are additionally analyzed. Experimental design strategies were used for the optimization of PIM composition and evaluating competitive transport. Synthetic seawater with 35% salinity, commercial seawater collected from the Gulf of California (Panakos®), and seawater collected from the beach of Tecolutla, Veracruz, Mexico, were employed. The results show an excellent separation behavior in a three-compartment setup using two different PIMs (Aliquat 336 and D2EHPA as carriers, respectively), with the feed phase placed in the central compartment and two different stripping phases placed on both sides: one solution with 0.1 mol/dm3HCl + 0.1 mol/dm3NaCl and the other with 0.1 mol/dm3HNO3. The selective separation of Pb(II), Cd(II), and Zn(II) from seawater shows separation factors whose values depend on the composition of the seawater media (metal ion concentrations and matrix composition). The PIM system allows S(Cd) and S(Pb)~1000 and 10 < S(Zn) < 1000, depending on the nature of the sample. However, values as high as 10,000 were observed in some experiments, allowing an adequate separation of the metal ions. Analyses of the separation factors in the different compartments in terms of the pertraction mechanism of the metal ions, PIMs stabilities, and preconcentration characteristics of the system are performed as well. A satisfactory preconcentration of the metal ions was observed after each recycling cycle.