I use a thunderbolt 3 dock with has a bunch of things plugged it into like a hard drive, mouse adapter, Topre keyboard, and a 4k screen. That's what the first thunderbolt port is used for. The second port is used for a second portrait mode screen alongside the 4k primary monitor. The third thunderbolt port is used for my DAC/AMP because I'm convinced the overall experience is better when plugged directly into the laptop rather than routing itself through a thunderbolt dock. The fourth port is occassionally used to attach accessories that I want directly plugged into the laptop for performance and stability reasons (thunderbolt 3 docks aren't are reliably as fast or as noise free as the ports on the laptop).
The laptop remains open, it is never in clamshell mode, because I like to use it as a third auxillary display for stuff like Slack, music, and other informational stuff. Also I frequently use Touch ID so leaving the laptop shut is not an option.
Both displays and the laptop are on separate floating monitor arms so I can move them around and out of the way if necessary.
For all intents and purposes my setup is identical to what it would be with a desktop machine. I could swap this MacBook Pro for a Mac Pro or Mini and have fundamentally the same experience minus the 'extra' screen from the MacBook and portability factor.