From the times I worked on very large rasters (several GB of aerial photography, in GIS or CAD softwares), I'd usually run into memory problems or paths problems.
If your system is running from an HDD instead of an SSD thats an easy culprit, especially since your files are much bigger than your RAM...
On the RAM side :
-check if you don't have apps/process clogging your memory
-could your RAM be faulty/mismatched/slow?
In your workflow, is your bitmap embedded or external? The latter could slow things, and I've faced problems when paths were too long.
The bitmap format may also be an issue, is it a compressed or uncompressed format?