Decontamination of water from antibiotic drugs or their metabolites using an adsorption technique represents a great challenge with respect to high adsorption capacity and cost effectiveness. Antibiotic drugs are generally released in water resources after human use, and these may be classified under the category of hazardous materials or persistent organic pollutants. Therefore, the present study is aimed to explore the removal of doxycycline (DCN) antibiotic drug by novel assembled chemically modified metal-organic frameworks in the form of NTiO2/NiSA-(Si-TETA)-Cu(II) nanocomposite. Effects of some parameters such as pH (2-10 range), contact time (1-60 min), nanocomposite doses (5-100 mg), drug concentrations (5-100 mg L-1), ionic strength (0.1-1.0 mol L-1 of NaCl), and reaction temperatures (25-55 degrees C) on the removal efficiency of DCN drug have been investigated, optimized, and evaluated. A complex formation between DCN drug and NTiO2/NiSA-(Si-TETA)-Cu(II) nanocomposite has been proposed as the contributing master mechanism, as carefully confirmed from the kinetics, isotherm, and thermodynamic studies. The kinetics and isotherm data were described by the pseudo-second-order and Langmuir models. The maximum identified adsorption capacity values were as high as 473.05, 562.08, and 682.15 mg g(-1) at 25, 40, and 50 degrees C, respectively. The removal efficiency values of DCN drug from water matrices by the action of NTiO2/NiSA-(Si-TETA)-Cu(II) nanocomposite were in the range 97.05 to 99.71% to elucidate that the NTiO2/NiSA-(Si-TETA)-Cu(II) nanocomposite can be applied for the removal of DCN drug from real wastewater samples.