Tweaking Doom III is still in its infancy, while as it is there are tons of guides out there with lots of useful info I wouldn't risk saying anything is 100% concrete once you leave the bounds of the standard 'known' tweaks (such as changing image quality and so on). That said the information below is here to help you optimise Doom III, read through it all and use what you think is necessary.

One thing I'd recommend to start is that you create a plain text file called autoexec.cfg and place it in the base folder. That way all your custom tweaks are in once place and are far easier to reference. Also please backup doomconfig.cfg before starting incase you make a mistake, the easiest way to restore your settings is to copy over a known-to-work doomconfig.cfg file and delete autoexec.cfg.