Zn-Al layered double hydroxide/zeolitic imidazolate framework-8 (Zn-Al LDH/ZIF-8) nanocomposite was synthesized through growing zeolitic imidazolate framework-8 (ZIF-8) on Zn-Al layered double hydroxide and employed as an effective pollutant adsorbent. The nanocomposite was utilized for the removal of Ifosfamide (IF) and cyclophosphamide (CK) anticancer drugs from aqueous matrices. Zn-Al LDH/ZIF-8 nanocomposite was characterized via different analyses such as Brunauer-Emmett-Teller, X-ray diffraction, X-ray photoelectron spectroscopy, Energy-dispersive X-ray spectroscopy, Elemental mapping, Fourier-transform infrared spectroscopy, Field emission scanning electron microscopy, Transmission electron microscopy, Thermogravimetric analysis, and Contact angle measurement. Batch experiments were implemented to investigate the parameters affecting the adsorption process, including adsorbent loading, pH value, ionic strength, initial pollutant concentration, temperature, and impurity. The experimental results were analyzed using various models to determine the adsorption mechanism, thermodynamics, isotherm, and kinetics. The Langmuir isotherm model presented higher consistency with the experimental data (R2 >0.990). The saturation adsorption capacity of the nanocomposite for IF and CK drugs, obtained as 929.66 and 888.94 mg/g, respectively, was found to be higher than those for ZIF-8 (759.70 and 724.53 mg/g, respectively) at a temperature of 298 ± 1 K and pH of 7.5 ± 0.1. The kinetic data had a better fit with the pseudo-second-order kinetic model (R2 >0.980). Thermodynamic studies revealed that the adsorption process was exothermic and spontaneous. The mechanism of adsorption was attributed to electrostatic interactions, hydrophobic forces, H-bonding, π-π stacking, and π-π electron-donor acceptor. Additionally, after performing four adsorption-desorption cycles, the nanocomposite indicated only a 9.3% reduction in the adsorption capacity, demonstrating the promising potential of this, for industrial applications.