At that point, you'll need to have multiple regions in play, and some sort of mechanism to direct traffic to regions when one becomes unreachable (for most people on AWS, this will be Route53).

Devil's advocate, though: if you're concerned about what to do in the event of an AWS regional failure, given how rare an event that is, then you've probably outgrown AWS.

(For most small-to-medium sized startups, I'd advocate setting up statuspage.io and keeping your users informed if you're single homed to an AWS region and that region experiences a catastrophic failure. The math on "how much money you'll lose from the outage" vs. "how much you need to spend implementing proper DR, better than what AWS has in place to keep a region up and running" isn't even close, assuming, say, 1 8 hour regional outage every ~2 years.)