In this study, the effective removal of three major micropollutants (e.g., propranolol hydrochloride, 1-naphthylamine, and 2-naphthol) from water is investigated using defected UiO-66 and functionalized derivatives as adsorbents. The defects in UiO-66 are induced using two distinct strategies. The first one involves a process of selectively thermolyzing labile linkers, leading to the creation of a hierarchical mesoporous framework (HP-UiO-66). The second technique employs monocarboxylic acid modulator, such as acetic acid (AA) or trifluoroacetic acid (TFA), which is coordinated with the Zr-clusters during synthesis and removed upon activation, resulting in the creation of defective UiO-66 structures. The influence they have on structural features of metal− organic framework (MOF) nanocrystals is compared to the ideal nonmodulated UiO-66 MOF. The samples are fully characterized by powder X-ray diffraction (PXRD), scanning electron microscope (SEM), Brunauer−Emmett−Teller surface area analyzer (BET), and thermogravimetric analysis (TGA). Their effectiveness as adsorbents for the elimination of 1-naphthylamine, propranolol hydrochloride, and 2-naphthol from water is examined. The thermodynamic and kinetic parameters of the adsorption process are determined. Interestingly, among the UiO-66 samples examined, HP-UiO-66 exhibits remarkable adsorption capacities of approximately 743, 602, and 409 mg g −1 for 1naphthylamine, propranolol hydrochloride, and 2-naphthol, respectively. These values surpass all of the reported adsorbents in the literature. The surface interactions between HP-UiO-66 and the three micropollutants were demonstrated by Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) analyses. This enhancement in adsorption performance is linked to the preferential adsorption mechanism, primarily by binding to coordinatively unsaturated zirconium atoms within the MOF structure. Through this study, an effective method for improving the adsorption capability of MOF-based adsorbents is presented through defects engineering in Zr-based MOFs. These findings open the path for the creation of effective MOF adsorbents for water treatment applications.