It is significant to investigate the photon transmission resilience of different glasses in order to identify the role played by each chemical unit therein and identify the radiation protection functionality of such glass systems. The role of V2O5 in dictating the optical and radiation transmission ability of (15-x)Li2O-70B2O3-15ZnO-xV2O5 glasses is investigated in this report. Extensive optical parameters which include: molar refractivity (Rmol.), metallization criterion (M), molar polarizability (αMol.), optical transmission (TOpt.), static dielectric constant, εstatic, reflection loss (RLoss), and optical dielectric constant, εoptical of the studied glasses were theoretically calculated. The mass attenuation coefficient MACg of the investigated glasses for 15 keV to 15 MeV photons was simulated through the FLUKA Monte Carlo simulation code and XCOM. Also, the fissile neutron removal cross section ΣR was estimated theoretically using the partial density method. Obtained results indicated that he Rmol. and αMol. of the LBZV glasses were enhanced with increment in V2O5 concentration; increasing from 16.892 to 19.869 cm2/mol and 6.703 × 10−24 to 7.885 × 10−24 cm3 respectively. Other estimated optical constants showed variations that appear to be strongly dictated by the amount of V2O5 in the glass chemistry. MACgdata from FLUKA simulations and XCOM calculations resonate well with each other. The MACg lies in the limits of 0.02–13.418 cm2/g, 0.018–13.848 cm2/g, 0.020–14.182 cm2/g, 0.02–14.367 cm2/g, and 0.019–14.772 cm2/g for increasing V2O5 concentration. The absorption parameters show that the V2O5 plays a positive role in the ability of the glasses to absorb gamma photons.