Police are investigating a fatal collision on the Burwood Highway, Upper Ferntree Gully about 8.40pm.
It is understood a car and bus collided on Burwood Highway, near the intersection of Mount Dandenong Tourist Road.
The driver of the car, who is yet to be formally identified, was pronounced deceased at the scene.
The driver of the bus was not injured.
There were no passengers on the bus at the time of the collision.
Police are working to establish the exact circumstances of the collision and investigations are ongoing.