Hydrokinetic tidal energy is one of the few marine renewable energy resources with sufficiently mature technology for commercial exploitation. However, several parameters affect its exploitability, such as the minimum speed threshold, ambient turbulence levels, or tidal asymmetry, to name but a few. These parameters are particularly important in regions with lower mean speeds than those in first-generation sites, such as the North Sea. The Gulf of California is one of those regions. In this paper, a Delft3D Flexible Mesh Suite (Delft3D FM) model in barotropic configuration is set up over the Gulf of California using a flexible mesh with resolution varying from O (500 m) in the deep regions to O (10 m) in the coastal regions. A simulation is run over the year of 2020, with a tidal forcing of 75 components. The model is validated at four tidal gauge locations and four Acoustic Doppler Current profiler (ADCP) locations. The speed, U, and tidal power density (TPD) indicators used for the validation were the annual means, the annual means for speeds above the 0.5 m s−1 threshold, the annual means of the spring tide maxima, and the annual maxima. The contour maps of the annual means, that is, the annual means for speeds above the 0.5 m s−1 threshold, allow us to identify tidal energy hot spots throughout the Gulf of California, particularly in the Great Island region (GIR). In this region, these hot spots have higher U and TPD values, in agreement with previous studies. The patterns of circulation around Tiburón Island and San Esteban Island on the East, and Ángel de la Guarda Island and San Lorenzo Island on the West, the four islands in the region with the highest tidal energy potential, are also discussed while recognizing that Tiburón Channel, between Tiburón Island and San Esteban Island, has proved to be the best siting location, based on the technical results obtained so far. The hot spots sites are further characterized by computing the tidal asymmetry in these small regions, showing the locations of the sites with smallest asymmetry, which would be the best for tidal energy exploitation. The hot spots around San Esteban Island are particularly important because they have the largest TPD in the GIR, with the model predicting a TPD on the order of 500–1000 W m−2. Here, complementary field measurements obtained with two ADCPs, close to San Esteban Island, one at 15 m depth, SEs (shallow region), and the other at 60 m depth, SEd (deep region), produced TPDs of 1200 W m−2 and 400 W m−2, respectively. The analysis of the vertical profiles and the tidal asymmetry over the vertical shows the importance of developing 3D models in future investigations.