Liquisolid powder compacts (LSPs) have demonstrated their ability to enhance solubility, thereby enabling the effective oral delivery of several drugs from Class II and IV of Biopharmaceutics Classification System (BCS). Our objective in this study was to develop and assess an orodispersible liquisolid compact containing Vardenafil hydrochloride trihydrate (VHT), with the aim of enhancing the dissolution characteristics of VHT through the utilization of a straightforward, scalable, and economical liquisolid compact technique. Different liquid vehicles for instance PEG400, Tween 20, PEG200, Tween 80 and propylene glycol were investigated in solubility studies. Among them, PEG400 (non-volatile solvent) was preferred in order to formulate the LSPs. For the quality-based design, process attribute optimization studies were done using 32 full factorial study design. The effect of % drug concentration (X1) and super disintegration concentration (X2) on response drug release percentage (Y1) and disintegration period (Y2) was evaluated with Design Expert (Stat ease Version 9.0.3). The results obtained from fourier transform infrared spectroscopy (FTIR) studies indicated the absence of any interaction among the polymers used and the drug moiety. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) Scanning Electron Microscopy (SEM) analyses provided evidence of the change of the VHT from crystalline nature to an amorphous form. The utilization of the Vardenafil hydrochloride trihydrate liquisolid method proved its efficiency in improving the dissolution profile and biopharmaceutical characteristics of a drug with limited solubility in aqueous media.