This book plays with the history of the X-men. A lot of the things that we know about their future and their past have been altered in some way, shape or form. It starts talking about year zero which was the "dream" Charles Xavier had about a world where humans and mutants are equal. Year Ten was the "World" that was made for mutants. Year one hundred was the "War" between mutants and machines and year one thousand was the "Ascension" of mutant kind.
There's a point where we pick up with Charles Xavier or at least a version of him from years back where he's talking to Moira Mactaggert. She asks him to read her mind and he seems confused.
We then pick up in the present day with Mystique and Toad who in House of X #1 escaped back to the mutant nation of Krakoa after escaping Damage control with stolen information. The present day is what is considered year ten. This means that it's been 10 years since Charles Xavier founded the X-men which delves into comic timelines. It turns out that he information they were stealing was for Magneto and Charles Xavier.
Xavier starts talking about how if someone wants a better world then they need to give something.
We then skip all the way to the future around year one hundred. We all know that mutants are destined to become the dominant species on Earth in twenty years. The events taking place one hundred hears in the future portray mutants being hunted down by the man machine supremacy. The mutant studying organisation of Orchis has got their way and by creating the supremacy, mutants are going extinct.
There is a resistance consisting of but not limited to a woman named Rasputin and a red skinned man called Cardinal.
These two were part of the Sinister line. The idea was first thought up by Mr Sinister. They were created to be controlled and used as mutant weapons. They were originally created as Krakoa's personal defense force and are descendants of first generation mutants that were genetically created. It turns out that Cardinal is part of a fail rate batch of these mutants that wanted to be pacifists and who all took on the name Cardinal.
Where as Rasputin is part of a successful batch. Sinister betrayed Krakoa though and was publicly executed by the man machine supremacy. Rasputin is trying to save a fellow mutant and she's giving it her all.
The mutant is captured though and she's taken to the human machine monolith. The person sitting in the seat of power is Nimrod. His adviser is Omega Sentinel.
This brings up the subject of what Orchis had to become in order to cut down the mutant population. There is also the mystery of why Nimrod is being so polite since he has a reputation of being a very unpleasant person. He even goes as far as to give his condolences to the mutant Sylabelle since she was a result of the sinister line. They want to interrogate Sylabelle but she was genetically engineered to resist all forms of interrogation and torture. That's when Nimrod has an idea.
They connect Sylabelle to a machine that will absorb the contents of her brain and apply her knowledge to huge assortment of Mutant minds that they've collected to help them win the war. We then time jump to Year one thousand. Someone called the librarian is frightened because he's losing the mutants in the hive mind created to win the war. Since we're year one thousand the war ended a while back.
He starts talking about these relics that they've kept since the beginning of the war to remind people of what they used to be and to move past that. He overlooks a glass sphere. That sphere contains some of the last humans.
It turns out that most mutants are now living with the Shiaar empire and are at constant war with the Badoon. We then travel back to year one hundred on the remains of Krakoa which only lasted thirty years according to the comic. Rasputin and Cardinal meet up with a familiar face. Wolverine.