Perth to Melbourne

It depends how long you are planning to do it over.

A friend did it over 3 weeks and had an amazing trip, stopping off at various places spontaneously on the way.

I want to say roughly 2 and 5.5 ish, maybe a little younger.

They lived there and were relocating to Perth, so decided to have a bit of an adventure, rather than just fly.

I’ll see if I can get some tips from her - she never once said “never again” so it can’t have been that bad

That's a lot of driving with little kids. Either do it in very short stages with an overnight stop at each roadhouse or just do pedal to the metal Norseman to Port Augusta and suffer it. Phenergan would be your friend here.
I think, for me, it would depend where the seatbelts were. If there was space for a parent beside the child seats, not so bad as interaction could take place. If the parents were up the front (belted in of course) and the kids isolated elsewhere, even if just behind, for long periods of the day, my heart would break as they would be so unhappy.
Also, what tie of the year would you be looking at?

Well, you will mostly have the wind behind you, so that's something. The days may be nice or may not be. The nights will range from cold to very cold. eg www.bom.gov.au/climate/dwo/201810/html/IDCJDW3005.201810.shtml
I say all this from having done a campervan trip at the same time of year Mel-Canberra-Mel when dd was 7. DH doesn't want to do it again but DD and I would like to very much.

You might want to check school holiday dates, particularly for accommodation at roadhouses on the Nullabor. Other than that, you should be ok.

Let me know if you have any other questions.