A Double Multiple Stream Tube (DMST) routine to predict the performance of cross-flow hydrokinetic turbines in real environments is presented, along with a site assessment application to identify the most efficient turbine aspect ratio, solidity and configuration (single, or paired) for a selected area of the Northern Adriatic Sea. The peculiarity of this DMST tool is its 3D character, since it allows to reproduce the vertical distribution of the torque generated by the turbine. To this end, correlations for fluid dynamic phenomena, based on high-fidelity fully CFD simulations, were implemented. The marine circulation code SHYFEM is adopted to obtain velocity profiles for a half lunar cycle period. The sites with the highest mean kinetic power were identified. The DMST routine is equipped with an iterative process able to establish which rotational speed maximizes the power output. Indeed, a spatially non-uniform velocity profile requires to determine the flow velocity more suitable to obtain the rotational speed via Tip Speed Ratio (TSR) definition. To this end, the section of the blades working at optimal TSR varies from top to bottom, until the maximum power is reached. It works as a virtual Maximum Power Point Tracking system able to adapt the turbine operating conditions for the different turbine geometries, and for changes in flow conditions. The results show that for the case study, the performance curve shape influences the optimal TSR blade section: the latter is often located in the upper part of the turbine for the low solidity, whereas, for high solidity turbines, in the bottom half part.