In this study, the rejection of three heavy metals (Pb, Zn, and Fe) was optimized using a polyvinylidene fluoride (PVDF) ultrafiltration membrane system combined with carboxymethyl cellulose (CMC) as a complexing agent. The fabricated PVDF membrane was characterized before and after filtration by FTIR, XRD, SEM, and EDX to ascertain the physicochemical properties. The PVDF ultrafiltration system integrated with CMC complexation was modeled and evaluated for the removal of Pb, Zn, and Fe metal ions using the response surface methodology (RSM)- Box-Behnken design (BBD). The RSM- BBD design was applied to determine the influence of three independent experimental parameters, i.e., pH, metal ions concentration, and CMC dosage. The proposed RSM model better described the experimental results with high R2 values (> 0.90) for all three metal ions. The optimized process parameters obtained by RSM showed that the maximum rejection % of Pb (101.28), Zn (89.74), and Fe (99.05) was achieved at solution pH of 7.64, 6.72, and 4.23, with initial metal concentrations 27.62, 20.46, and 133.15 mg/L, and CMC dosage 1.99, 0.14, and 0.46 g/L, respectively. The PVDF-membrane integrated CMC ultrafiltration system demonstrated good reusability with a reduction of only 5, 40, and 31 % for Pb, Zn, and Fe, respectively, after three consecutive cycles. The results indicated that integration of CMC complexation with PVDF ultrafiltration system is a promising approach for enhanced rejection of heavy metals from water.