Marie returns as a major player in Splatoon 2's hero mode in Octo Canyon. This time, she is more open about her identity as Agent 2 and fills Cap'n Cuttlefish's role as Agent 4's main advisor and guide, as the Cap'n is out on a research trip with Agent 3. As Agent 4 fights through the Octarian complex in search of the Great Zapfish, Marie reveals to the player that Callie went missing at the same time as the Great Zapfish, and suspects Octarian involvement. After beating the The Octo Shower, she and Agent 4 receive a call telling them to leave Octo Canyon and never look back. However, Marie quickly realizes that the caller is Callie due to the fact that the caller is holding the phone upside down (a recurring gag in the original Splatoon single player). In the final boss battle, it is revealed to the player and Marie that Callie has been brainwashed by DJ Octavio using his hypnoshades and are forced to fight him and Callie; as the battle continues, Marie is able to shoot off the hypnoshades with a Hero Charger filled with "Low-Tide Ink", slowly bringing Callie back to her senses. When Callie finally makes a full recovery, Marie is able to pull out a boom box playing Calamari Inkantation, allowing them to distract DJ Octavio and letting Agent 4 to finish him off, saving the Great Zapfish.