Fexofenadine HCL (FEX) is an antihistamine that has inadequate oral bioavailability and limited aqueous solubility. The goal of this work is to develop and evaluate FEX nanosuspensions integrated into oral fast-dissolving films (OFDFs) to improve drug bioavailability. FEX nanosuspension was generated by an antisolvent-precipitation approach using a full factorial design (32). The influences of stabilizer content and the ratio of solvent-to-antisolvent on the particle size and relative dissolution rate were investigated. The optimized formula showed an average size of 57.3 nm with the relative dissolution rate of 4.42. Such formula was evaluated for FT-IR, DSC, XRD and morphology. The FT-IR studies appeared no chemical interaction between FEX and stabilizer. The crystallinity of FEX was reduced as detected by DSC and confirmed by XRD. SEM revealed that FEX-nanosuspensions had a rod-like appearance. The optimized FEX nanosuspensions were then directly loaded into OFDFs throughout a solvent casting process. The influence of the CMC and SSG concentrations on disintegration time and dissolution efficiency % after 10 min was detected using Statgraphics® software. The optimum FEX-OFDF prepared with 1% w/v CMC and 2.68% w/v SSG showed a disintegration time of 21.74 s and a dissolution efficiency of 79.23% after 10 min. The optimized formulation of FEX-OFDF increased the oral bioavailability of Fexofenadine hydrochloride by 4.15-fold when evaluated in rabbits compared to commercially available Telfast® tablets.