Autodesk Simulation CFD has the ability to handle multiple fluids in one model. Note that fluids with different fluid materials cannot contact one another unless one or more is a distributed resistance. Non-distributed resistance fluids can be connected thermally (separated by a solid material).
To implement multiple fluids, assign the fluid materials as appropriate, and ensure that different fluids are separate by solids or voids.
Examples where this is useful include an air-water heat exchanger or flow blown over a sealed electronics component box. In the latter example, natural convection might be important inside the sealed box, and forced convection may play a role outside the box.