In the current work, neodymium oxide (Nd2O3) nanoparticles were synthesized and characterized by means of X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The major aim/investigation of this research was to fit/model and optimize the removal of Acid Blue 92 (AB92) dye from synthetic effluents (aqueous solutions) using the adsorption process based on neodymium oxide (Nd2O3) nanoparticles. To optimize the adsorption conditions, central composite design (CCD) based on response surface methodology (RSM) was applied. The effects of pH (3–9), adsorbent dosage (0.1–1 g/L), initial concentration of AB92 (100–300 mg/L), and contact time (10–100 min) on the adsorption process were investigated. Apart from equilibrium and kinetic experiments, thermodynamic evaluation of the adsorption process was also undertaken. The adsorption process was found to have the best fitting to Langmuir isotherm model and pseudo-second-order kinetic equation. Also, the process was found to be spontaneous and favorable with increased temperature. The optimal conditions found were: pH = 3.15, AB92 concentration equal to 138.5 mg/L, dosage of nanoadsorbent equal to 0.83 g/L, and 50 min as contact time, which resulted in 90.70% AB92 removal. High values for the coefficient of determination, R2 (0.9596) and adjusted R2 (0.9220) indicated that the removal of AB92 dye using adsorption can be explained and modeled by RSM. The Fisher’s F-value (25.4683) denotes that the developed model was significant for AB92 adsorption at a 95% confidence level.