In natural convection (high Richardson number Ri), a high Prandtl number (Pr) leads to thinner thermal boundary layers, enlarging the thermal gradient and hence the enhancement of buoyancy effect. In forced convection (low Ri), a high Pr introduces thicker velocity boundary layers. In mixed convection scenarios, where both forced and natural convection are significant, the interaction between Pr and Ri determines the resultant flow pattern and heat transfer characteristic. Three tandem circular cylinders with an identical spacing ratio of 4.0 in both forced and mixed convection flows were numerically investigated by using finite element method. The computations were carried out in the range of Pr = 5–50 and Ri = 0–2 at a low Reynolds number of Re = 150. The results of the squared strain rate and the vorticity shed light on the enstrophy transfer process. Thermal plume structures in the far wake originate from the upper dispersed vortices due to the high superimposed buoyancy at low Pr, while they are suppressed at high Pr. The increase in Pr plays a role as the flow stabilization, while the growth of Ri plays the reverse role. The time-averaged velocity, pressure coefficient, and temperature become more asymmetrical at high Ri. The Nusselt number of the upstream cylinder is approximately equal to the empirical result without the consideration of thermal buoyancy. Due to the thermal buoyancy, the migration of shear layers along the cylinder surface leads to the frequency alteration and harmonic frequency in the drag, lift, and Nusselt coefficients.