Detection of volatile organic compounds (VOCs) is one of the most challenging tasks in modelling breath analyzers because of their low concentrations (parts-per-billion (ppb) to parts-per-million (ppm)) in breath and the high humidity levels in exhaled breaths. The refractive index is one of the crucial optical properties of metal-organic frameworks (MOFs), which is changeable via the variation of gas species and concentrations that can be utilized as gas detectors. Herein, for the first time, we used Lorentz–Lorentz, Maxwell–Ga, and Bruggeman effective medium approximation (EMA) equations to compute the percentage change in the index of refraction (Δn%) of ZIF-7, ZIF-8, ZIF-90, MIL-101(Cr) and HKUST-1 upon exposure to ethanol at various partial pressures. We also determined the enhancement factors of the mentioned MOFs to assess the storage capability of MOFs and the biosensors’ selectivity through guest-host interactions, especially, at low guest concentrations.