While dying the same as in the series, being burned at the stake by Duchess Gertrude, as a spirit, Isobel is nye unstoppable, though she can be defeated through bargaining and others. She usually leaves the way she did in the series, resting in peace after killing Genevieve Teague.
After compelling Lana to go to China and look for the Stone of Air, Isobel possessed Lana again and grabbed Lois' neck, allowing Brianna to repossess her. She then tells her that they have a crystal to find and denying Brianna's idea of her kissing Bruce Wayne first. She also insists that Brianna stay calm as they won't be corporeal forever. She then leaves Bruce and Clark, pulling Brianna away from Bruce. The two then run into Jason Teague as Isobel angrily lifts Jason up by his neck for what Duchess Gertrude did to her. When Clark arrives to stop her, Isobel recognizes Clark as Kal-El. Isobel still tries to pretend to be Lana, but Clark and Bruce don't fall for it, the two teleport off with Jason as Isobel prepares to drop Jason off a cliff, declaring who she is to Jason and telling Brianna to be quiet when she asks for Bruce Wayne's number, claiming she has the attention span of a child. When Jason says he's looking for the Stone, Isobel demands that it's hers, though Brianna points out that it technically belongs to Clark before Isobel silences her. However, Clark saves Jason and confronts the two with Bruce, with Isobel explaining that Lana and Lois still exist but are basically sleeping. She also stops Brianna from making an advance on either of them. Isobel demands to know where the Stone is, and while Clark says he doesn't know, he demands that she let Lana go. Isobel refuses and blasts Clark and Bruce back. Before the fight can escalate, Bruce tosses down a gas pellet as they escape in the confusion, with Isobel saying plainly that Bruce only knows how to disappear. She then decides to shadow them with Brianna, literally. The two then return to normal after Clark and Bruce find the stone in a museum exhibit filled with Blue Kryptonite. Isobel recognizes the Blue Kryptonite as something other than sapphires. Isobel then stops Brianna from making an advance on Clark. She then demands Brianna to focus as she keeps fooling around. Isobel then explains that she's out for revenge against the Teagues for killing her and Brianna. When Bruce says vengeance solves nothing, Isobel brushes it off considering Bruce's past. Isobel is then knocked in the head by a sword Bruce takes from the exhibit. When Isobel shouts at Brianna again to focus, and Clark knocks her out, Isobel blasts both of them back as she goes to stab Clark with a sword. However, Bruce knocks her out as the Stone of Air restore Lois and Lana back to normal, ending Isobel's threat, for now.