- "I will march to Wayne Manor, I will drag your faithful butler onto the streets of Gotham and I will make him tell the world how you failed."
- ―Hugo Strange to Batman[src]
In Cold, Cold Heart, Mr. Freeze and the Penguin's Henchmen invaded Wayne Manor on New Years Eve and were looking for Ferris Boyle during the Humanitarian of The Year Awards Ceremony. Bruce found himself fighting through his own home with the help of Alfred in his earpiece communicator. Bruce had originally planned to access the Batcave via the Study, although the presence of reporters in the Study resulted in him accessing the Batcave via the Wine Cellar behind a wine rack, that was accessible via a statue lever, and also traversed carefully through the path due to it still sustaining damage from Bane's earlier attack on the Batcave on Christmas Eve. Once in the Batcave, he suited up as the Dark Knight and returned to the manor. However, the manor ended up being torched by the Penguin's men on orders from the Penguin himself, as revenge against Bruce for the latter's family ruining his own family, the Cobblepots. Batman rescued a captured Alfred, Vicki Vale and several other hostages from the thugs in the Library and pursued Freeze.
Aside from the Ballroom and the Study, Wayne Manor also contained a Library and a Wine Cellar, the latter of which contained various expensive wines including Bordeux-brand wine and a Wine-Tasting Room. The Library also contained some artifacts, including a display of the pearl necklace that Martha Wayne had worn on the night she and Thomas were murdered at Crime Alley. It also contained a golden skull and a red rotary phone.
Wayne Manor appeared in the Nightwing DLC Pack, containing a Combat Map (Wayne Manor Armory), and a Predator Map (Wayne Manor Main Hall). TYGER Security were in the Combat Map and the Joker's Henchmen were in the Predator Map.
In the alternate Catwoman ending, Barbara Gordon proclaimed that Joker's army had taken over Gotham City and that Wayne Manor was compromised. Batman and Commissioner Gordon were dead in the alternate ending, but thankfully, the game rewound the sequence so that Catwoman could make the correct decision and save Batman.