The cars collided near the Stud Road off ramp just after 2pm police said.
Five people were taken to hospital, including an adult and boy from one vehicle who are in a critical condition.
The boy was rushed to the Royal Children’s Hospital and the woman in her 40’s taken to The Alfred.
Both have injuries to their upper bodies.
All out-bound lanes and one in-bound lane of the Monash Freeway are closed.
Police are investigating.