Revealing the controlling effect of geological structure on seafloor hydrothermal activities is of great significance in understanding the formation mechanism of hydrothermal system and searching for seafloor sulfide resources. This article summarized the topography and faults, crustal structure, gravity and magnetic field, heat flow and magmatism in the middle and southern Okinawa Trough, as well as the general characteristics of hydrothermal field distributions and hydrothermal products. By comparing the Okinawa Trough with the Manus Basin, Mariana Trough, North Fiji Basin and Lau Basin with different rock basements and extension stages, we generalized some specific geological characteristics of the Okinawa Trough, including the transitional crustal nature, low extension degree, high heat flow value, extremely thick sediments, and bimodal volcanism. The hydrothermal activities in the Okinawa Trough are controlled by fault structures, magmatism, and spreading rate, and at the same time, are affected by basement rock types and sediment covers. In the middle and southern parts of the trough, two group of faults that are parallel and perpendicular to the strike of the back-arc basin promote the fluid circulation, and large-scale magmatic activity provides sufficient heat for the hydrothermal system. In addition, the interaction of fluids with the widespread silicic volcanic rocks and thick sediments leads to the enrichment of organic matter, CO 2, and metals such as Ag and Au in the hydrothermal products. According to the extension rate and geological features of the Okinawa Trough, we believe that the Okinawa Trough has potential to have new hydrothermal fields discovered and we speculate that new hydrothermal fields most possibly exist in the regions influenced by ridge subduction as well as the neo-volcanic zones closed to the island arc.