Sam wasn't the only vessel that was meant for Lucifer. There is also his sister. After being raises by demons and monsters, for her entire life, one demon hands her over to her brothers.
While researching a demon attack in Massachusetts, Sam and Dean stumble across a plot to free a demon more powerful than Lucifer himself. With the help of a hunter they meet and a demon that seems to be on the same side they are, they try and stop the demon from rising.
It's not that easy: the plans to free Onith from Hell have seemingly been kickstarted. If he rises, he will destroy the universe.
There is only one way to stop him once he has risen: Sam's psychics. And to stop Onith means turning into a monster himself.
Are they prepared to sacrifice Sam to stop Onith, or is there another way?