Contamination of water by heavy metals is a worldwide environmental problem where industrial activities are the major contributor to this pollution. Contamination of heavy metals may lead to various toxic effects towards human and environment, so it is very important to find the most suitable treatment for this problem. Conventional method to treat heavy metals contamination in water and wastewater is costly, caused detrimental effects towards the affected area and high sludge production. Therefore, a cheaper and more effective alternative to conventional treatment, which is phytoremediation, one of the biological treatments is studied. This study aims to determine the efficiency of A. puber planted in constructed wetlands (CW) microcosm to remediate wastewater contaminated by heavy metals. Synthetic wastewater containing heavy metals i.e. Cd, Cr, Cu, Ni, and Zn were used for the preliminary study and response surface methodology (RSM) with central composite design (CCD) was applied to optimize the remediation process. Two operational variables, hydraulic retention time (HRT) (2, 7 and 12 days) and initial Ni concentration (5, 52.5, 100 ppm) were studied. Characterization of heavy metal absorption by A. puber was also studied using FTIR, FESEM and TEM. In the preliminary study, Ni showed the highest removal efficiency compared to other metals tested and the transfer of metals in plants parts were evaluated as translocation factor (TF). TF was less than 1 for all heavy metals tested where this confirmed the significance of roots as heavy metals accumulator compared to leaves and stems. Optimization study indicates that 95.6% Ni removal can be achieved with HRT of 10 days and 100 mg/L initial concentration with high correlation coefficient (R2=0.97) between the model and the experimental data. Characterization by FTIR analysis shows that Ni ions may be coordinate with the hydroxyl, amide, and amino groups present in A. puber, meanwhile, FESEM and TEM images show some changes for A. puber sample due to Ni exposure. This study has demonstrated that A. puber planted in CW microcosm is suitable to remediate wastewater contaminated with Ni.