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Following the defeat of Doctor Psycho and Kite Man leaving Ivy, Harley and Ivy became a couple with Ivy planning to turn Gotham into a rainforest. Harley offers to help, and together, they mutate Frank into being capable of resurrecting plants.
However, Bruce discovers this and has Frank abducted. With this, Harley and Ivy are forced to find out who kidnapped Frank before discovering Bruce to be the culprit. While there, Harley has a run in with Batgirl again, and the two of them are captured by the Mad Hatter. Due to Harley being a fellow villain, Hatter is willing to let her go. At first, Harley gets ready to leave Batgirl to her fate, but she eventually grows a conscience and goes back to save her and also kill the Mad Hatter just to contradict Batgirl's statement of her being merciful.
Eventually, Harley and Ivy manage to capture Bruce but are unable to make him talk. Because of this, they are forced to get Doctor Psycho to help them enter Bruce's mind where they discover he is trapped in the same memory of his parents dying. Harley assumes that preventing the trauma would allow them to progress, so she makes an attempt to kill the killer. When that proves ineffective, she has young Bruce look away, forcing Psycho and Ivy out while Harley has to protect young Bruce as they delve deeper into his mind.
As she progresses, she soon finds out Bruce to be Batman before entering a memory she remembers of when she was blindingly loyal to the Joker, much to her disgust (while forced to take on the role of Robin in said memory). As she fights her past self, she begins to enjoy playing the role of a heroine. Eventually though, Harley realizes that she can't help Bruce get past his trauma from within his mind, and promises to help him and keep him being Batman a secret.
Upon leaving Bruce's mind, she finds herself tied up with the rest of her crew as Bruce uses Frank to revive his dead parents, which results in a zombie apocalypse. With the zombies overrunning Gotham, Harley teams up with the Bat Family to stop it while Ivy tries to awaken the power to stop this. Instead though, Ivy decides to use the power to control the zombies and take her plan in a different direction. Seeing this, the Bat family propose the need to kill Ivy.
Not wanting them to do such, Harley asks them to let her talk to Ivy. Seeing just how set Ivy is on this plan despite how many innocent people are getting hurt, Harley jumps in the way of some zombie puke (saving Bane by coincidence), forcing Ivy to choose to abandon her plan or leave Harley behind. Ivy refuses to go on without Harley and turns Gotham back to normal with the zombies becoming lifeless again.
Harley expresses desire to make it up to Ivy, so when Lex Luthor offers to make Poison Ivy the new leader of the Legion of Doom on the demand of killing the Joker, Harley offers to take part. However, Ivy notices some unusual details which even the Joker points out to her. Eventually Ivy realizes that Harley is forcing herself to be evil for her sake and talks her down from actually killing the Joker. Harley says that she doesn't want to lose Ivy, so Ivy assures her that they will be together whether Harley is a hero or a villain even if they are on opposing sides. With this settled, the Joker is let go, and Bruce Wayne is arrested for tax evasion. Harley assures Bruce that she will still provide him her mental help as she promised.
Later, she joins the Bat Family on their patrol of protecting Gotham.