The effect of polar and non-polar solvent combinations on a high moisture barrier coating film composed of an epoxy–acrylate hybrid resin was determined with the aim of promoting its application in flexible device applications. More specifically, the epoxy–acrylate hybrid resin was formulated using various solvent combinations and was manufactured via ultraviolet (UV) and thermal curing. An outstanding barrier performance and excellent thermal and mechanical properties were observed when the resin was prepared using solvents with a small gap between their solubility parameters and at high vapor pressures. This was attributed to an increase in the polymerization degree of the epoxy resin in the absence of residual solvent. In addition, the water vapor transmission rate (WVTR) of a polyethylene terephthalate (PET)/polymer/SiNx multi-layered film was also influenced by the solvent employed for the coating solution, wherein a combination of acetone/toluene was optimal. This solvent system possessed a small solubility gap (i.e., 0.057), resulting in a WVTR of 1.17 × 10−2 g/m2·d after the deposition of a 50 nm layer of SiNx. Notably, this WVTR is >2-fold lower than that obtained for the ethanol/toluene combination with a large solubility constant difference > 5.0. These findings highlight the importance of the polymer coating solution composition in the preparation of multi-layer architectures to obtain effective inorganic barrier coatings.