When I'm traveling with my toolbox, it usually means I'm either on some sort of road trip or going to do volunteer trail work and I have a bunch of other stuff crammed in the back as well with the rear seats folded down. Because of all the extra stuff, the toolbox can't really shift anywhere or fall over.
If I were just carrying a toolbox and not much other gear, I would use a ratchet strap and use the built in tie down loops in the floor of the cargo area so the toolbox couldn't shift around or fall over.