Needless to say, this is only possible in a video game or Visual Novel.
And there are infinite possibilities.
You could, for instance, have your characters directly interact with the game itself. You could make traditional gaming concepts into actual parts of the universe.
- Exploiting the Fourth Wall: If you're going to play meta elements for drama, you'll need your villain to have powers related to the fourth wall.
- Noticing the Fourth Wall: At some point, the meta character(s) will need to realize the existence of the player. This can happen before the story (see Doki Doki Literature Club!, most routes), or during the story (also in Doki Doki Literature Club!, try deleting Monika before the start of Act 1 and watch what happens)
- Reality Warper: Obviously, having fourth wall powers makes someone so overpowered they can be considered a Mary Sue without question. Your villain should probably be some form of a Reality Warper, who will need similar levels of reality warping (either from in-universe or from you, the player) to defeat.
- Occurs twice in Undertale:
- The final boss of a neutral run has six save files to his name, and is more than willing to use them. He can only be defeated by making the SOULs he's using to save and load rebel against him.
- The final boss of a genocide run breaks all the typical rules of the game: he starts first (typically only you can do this), overrides your Invincibility Frames so he can be extremely competent despite having only 1 ATK, dodges every single attack so he can survive your One-Hit Kill attacks (he's the only monster who does this), attacking you in the menu, and going to sleep during his turn so you can't do anything. He has to be defeated by maneuvering the bullet box over to the Fight button.
- In Doki Doki Literature Club!, Monika deletes her potential romantic competition from the game so you can only choose her, then locks you in a room with her where she literally does nothing but talk. The only way to defeat her is to go into the game directory and delete characters/monika.chr, at which point she will have a Heel Realization and restore the other characters.
- Occurs twice in Undertale:
- The Fourth Wall Will Not Protect You: Otherwise, your player will utter the Eight Deadly Words and stop playing forever. That's not to say that you have to utterly trash the player's computer: Doki Doki Literature Club! was actually pretty tame by the creator's standard, because he didn't want to mess with your computer too much (which would make the game essentially a playable virus). Despite this, Monika still knows your name (she gets it off of your user account).
- Call a Hit Point a "Smeerp": Perhaps more descriptive names might be better for the traditional concepts.
- In Undertale, EXP and LV stand for Execution Points and Level of Violence respectively, which is fitting for a game about pacifism.
- He Knows About Timed Hits: A frequent manifestation of a fourth wall breaker is to use it to explain how to play.
- Interface Screw: A final boss that has powers over the fourth wall can suitably manipulate it to her tastes.