Novel glass systems with the compositions xNiO-20ZnO-60B2O3-(20-x) CdO (0 ≤ x ≤ 5 mol%) have been designed and assembled by the melt quenching technique from different nanometal oxides (NiO, ZnO, B2O3, and CdO) to serve as competitive candidates for radiation shielding. The X-ray diffraction technique was utilized to confirm the amorphous character of the samples. The target metal oxides (ZnO, NiO, CdO and B2O3) were synthesized in the nanoscale, as confirmed by SEM analysis. The mechanical properties of the new composites have been studied and their elastic moduli have been estimated. Enhancement in the elastic moduli, density and physical properties were achieved by the assembled systems. The density was varied between 3.72 and 4.27 g/cm3, whereas molar volume decreased from 22.51 to 19.53 cm3 mol−1, as the loading of NiO NPs increased from 0 to 5 mol% in the composite. The mass attenuation coefficients (µm) have been measured at different γ-ray photon energies (662, 1173 and 1332 keV) using narrow beam transmission geometry and the results have been compared with those obtained by XCOM simulation code to confirm a good match between the values. Measurements referred to the increase in some parameters of the new glasses, including the mass attenuation coefficient (µm), effective atomic number (Zeff) and effective electron density (Nel) due to the increase in NiO content from 0 to 5 mol%. Additionally, the half value layer (HVL) and the mean free path (MFP) were decreased with increasing NiO percent content. The achieved results denote that 5NiO-20ZnO-60B2O3-15CdO exhibited the best radiation shielding characteristics among the tested glasses. Finally, the radiation shielding characteristics of the new glass systems have been compared with the previously studied standard glasses to refer to the superiority of the assembled systems.