I know that makes no sense does it considering that didn't stop her with Dan, did it? What I should say is Serena and Chuck can probably do a lot of damage teaming up if they use their powers for evil :D
Never. They are the last two who haven't ever gotten romantic. And as much as people like to say Serena and Dan are siblings (they aren't and never have seen each other that way), Serena and Chuck see each other और as siblings. Their friendship is great the way it is and them getting together is a bad idea.