Wavy fins and vortex generators can separately enhance the thermal performance of heat exchangers. A novel combination of wavy fins and vortex generators is proposed in the present study to optimize the thermal performance of heat exchangers. The effects of the longitudinal vortices and attack angle of the vortex generators on the thermal performance of the novel combination are numerically studied. The longitudinal vortices are strengthened and weakened when the fluid flows over the crests and troughs of the bottom wall, respectively. The heat transfer on the pressure sides of both top and bottom wall surfaces is significantly larger than that on the corresponding suction sides. There is an optimal attack angle of 60°, which can provide the best heat transfer performance with a maximum 31.5% increase in the Nusselt number with only a 23.4% increase in the friction factor. The maximum thermal performance factor can be up to 1.23 with the optimal attack angle. Correlations for Nu and f are reported for both laminar and turbulent flows.