Sea waves energy represents a renewable and sustainable energy resource, that nevertheless needs to be further investigated to make it more cost-effective and economically appealing. A key step in the process of Wave Energy Converters (WEC) deployment is the energy resource assessment at a sea site either measured or obtained through numerical model analysis. In these kind of studies, some approximations are often introduced, especially in the early stages of the process, viz. waves are assumed propagating in deep waters without underneath ocean currents. These aspects are discussed and evaluated in the Adriatic Sea and its northern part (Gulf of Venice) using locally observed and modeled wave data. In particular, to account for a “state of the art” treatment of the Wave–Current Interaction (WCI) we have implemented the Simulating WAves Nearshore (SWAN) model and the Regional Ocean Modeling System (ROMS), fully coupled within the Coupled Ocean Atmosphere Wave Sediment Transport (COAWST) system. COAWST has been applied to a computational grid covering the whole Adriatic Sea and off-line nested to a high-resolution grid in the Gulf of Venice. A 15-year long wave data set collected at the oceanographic tower “Acqua Alta”, located approximately 15 km off the Venice coast, has also been analyzed with the dual purpose of providing a reference to the model estimates and to locally assess the wave energy resource. By using COAWST, we have quantified for the first time to our best knowledge the importance of the WCI effect on wave power estimation. This can vary up to 30% neglecting the current effect. Results also suggest the Gulf of Venice as a suitable testing site for WECs, since it is characterized by periods of calm (optimal for safe installation and maintenance) alternating with severe storms, whose wave energy potentials are comparable to those ordinarily encountered in the energy production sites.