Procedural Generation is more or less not an option either. Many have tried but none have so far actually brought any results to the table AFAIK.
Honestly, Blighted makes a semi-decent counterpoint I think.
Traditionally fredded sexp-scripted missions are going to be hard to adapt to this, but I think if one embraces lua scripting there's not much actually stopping 'open world' gameplay with distinct 'instances' you jump between, similar to EVE online, or indeed Blighted. You would essentially have to build a new larger scale gameplay loop, more in the design sense than just the programming sense, and track it's state via lua. Either do the mission logic purely in lua or have standard level files that act as a templates for different types of missions that you flesh out with lua data to generate different areas. If memory serves the campaign system is manipulable enough with lua to allow that, but I've never actually dissected any of the mods that push those boundries to see exactly how it's done.
It's also worth mentioning that if you have a specific vision and can identify the individual features, and are patient, you can often get holes in the engine support for your idea filled. If you try to make something like I just described but find that a couple of scripting functions or sexps you can't live without don't exist or a quirk of the engine is roadblocking, don't treat that as the death of the idea. If you tell the developers it might turn out that what you want is doable, or someone might have a clever alternative for you.