After the mission to Palaven and Grissom Academy, or just Sur'Kesh, Shepard gets a message from Miranda asking to meet on the Citadel at Docking Bay D24. Miranda expresses her concerns that her sister Oriana had been found by her father. If she is in a romance with Shepard, Miranda shows that she was greatly pained when Shepard was detained on Earth, and almost thought to break in to see him. If certain decisions are not made to warn her of a Cerberus attack, Miranda will later be killed by Cerberus Assault Troopers, under orders from the Illusive Man. To keep Lawson alive, Shepard must read the dossier Anderson forwards on Kai Leng, and warn her about him via video conference in the Spectre Office in the Citadel Embassies. Should Miranda not be spoken to before Cerberus' attack on the Citadel, Miranda will still send Shepard a message to contact her via the Communications Console in the Spectre Office in the Citadel Embassies.
She is later encountered on Horizon after Cerberus retrieves the Prothean VI from Thessia. Shepard quickly finds that Oriana is indeed being held by their father, who is operating a Cerberus facility disguised as a shelter called Sanctuary. Miranda is seen in recordings throughout the mission warning civilians of her father's true intent. Finally, Henry Lawson, who is holding Oriana as a human shield, comes face to face with both Shepard and Miranda. Shepard is either able to diffuse the situation diplomatically or to simply shoot him. If Shepard allows Lawson to leave, Miranda will refuse, using her biotics to push him out of a nearby window. Miranda, who was badly injured during a running battle with Kai Leng, dies in the company of Oriana and Shepard if she was not previously warned about Kai Leng's return to service of Cerberus. If Miranda's loyalty was not secured, or she was not given Alliance resources in an earlier conversation with Shepard, Kai Leng will mortally wound her even if warned.
If Shepard cannot persuade Lawson diplomatically and does not shoot him after diplomacy fails, Miranda will take the initiative to kill Lawson herself, but Lawson will manage to get in a shot that fatally wounds Miranda, causing Miranda to die even if Miranda was warned about both the Cerberus attack and Kai Leng's return to Cerberus.
If Miranda survived those events, she tells Shepard she had the time to place a tracking device on Kai Leng during their short encounter, allowing Shepard and the Alliance to find the Illusive Man's location. Miranda then leaves with her sister, and asks Shepard to be careful.