In this paper, thermohydraulic characteristics and enhanced heat transfer mechanism in water–cooling oil heat exchanger with various shapes and attack angles of vortex generators (VGs) and spacing of double VGs are numerically investigated at different Reynolds number (Re) and oil–water mediums. A CFD-aided method, conjugated heat transfer model, is performed to elaborate the correlation between heat transfer and flow characteristics. The quantitative and qualitative results manifest that the longitudinal and secondary vortices, induced by VGs, generate synergistically the tapered and elliptical enhanced heat transfer regions on the heat exchange fins, but the inhibiting effect still exists between both, particularly in high attack angle or oil medium. Elliptical winglet VG with 30° in oil medium with Re = 349 and 15° in water medium with Re = 2726 gains the maximum thermal performance factor, reaching 1.69 and 1.28, respectively, compared without VGs. Furthermore, the appropriate configuration of two core heat transfer regions is a cost-optimal method to obtain in-depth synergistic heat transfer. The spacing of 4 mm shows the best synergistic heat transfer, and the maximum heat flux of its was elevated to 2.2% and 8.6% more than that of single VG in oil and water medium, respectively.