Wow, rude of you to regift literally every gift that you or anyone else has ever received.
This comic was the Christmas comic of 2020 and was published on Christmas Day, a day where people who celebrate Christmas traditionally open presents.
In this comic, Megan is unwrapping a present while Cueball looks on (perhaps it's the present he gave her). The premise is that the definition of a present is not what's inside the box, but what's inside the region of space that the blank side of the wrapping paper faces. So if you wrap the box with the printed side towards the box, everything in the universe outside the box is the gift. Apparently, the box contains a pair of headphones, which would be a nice present, but not nearly as impressive as almost everything in the universe.[citation needed] And since the rest of the universe contains millions of headphones, many of which are probably nicer than the ones in this box, she still gets headphones as well.
The title text extends this to regifting, which is the practice of using a received present (usually unwanted and hopefully unused) as a present for someone else. This practice is often considered to be impolite because it's assumed to simultaneously show a lack of appreciation of a gift you've received (because you want to get rid of it), and an unwillingness to spend much time, effort, or money on a gift for someone else. But if you wrap an ordinary present inside out, all the gifts you've ever received in the past are part of the entire universe except for that present, so you're actually doing an enormous amount of regifting including stuff belonging to other people, which is as rude as regifting can get.
Douglas Adams's novel So Long, and Thanks for All the Fish, the fourth in the The Hitchhiker's Guide to the Galaxy series, contains a similar joke. A man living in an inside-out room in a desert treats the rest of Earth as an insane asylum, with himself living outside of it as the only sane man.
This may also refer to a math joke about how to create the smallest fence around a group of animals. Rather than finding the obvious fence, a mathematician would build a small, circular fence around themselves and declare the region on the other side of the fence "inside", thus enclosing all the animals!
The mention of headphones might be a reference to the AirPods Max, which were released by Apple on December 9, just 16 days before this comic, and stirred much debate for their USD$549 price tag.