After demolishing the castle, and eliminating the alien threat in time, Duke is ready for some R'n'R, unfortunately, the aliens aren't. In the castle, Duke faces the worst of the horrors the aliens have created, and finally confronts the alien general in charge of it all, a giant brain. Duke fights toward the castle, which the aliens have taken over (not before blowing up a Zeppelin). Zombies litter the streets, and Brains float in the air. In the Victorian Era, Duke is set upon by the biological weaponry the aliens have been manufacturing. Duke then is informed, that it's not just America's past that is being altered, the aliens have also been sent to the Victorian Era of London. There, he stops the mining project before the aliens can succeed.
After blowing up a ship containing the super-soldiers, Duke makes his way to the town of Roswell. The aliens have begun creating super-soldiers in order to combat Nukem and the humans of the future.
In the Old West, due to technical difficulties, Duke must make do with period weaponry with the exception of a few of his weapons which his allies can send back. Duke is sent back to the Old West, where aliens have taken over parts of the American West in an effort to mine out Earth for its resources. The humans have developed their own time machine in order to send a soldier back to re-write history, and destroy the aliens.
There, they tell him that the aliens are indeed screwing with history, so much that this future is just one, if Duke wants the old one back he'll have to fight for it. Duke eventually meets up with the small band of resistance fighters in the old headquarters of the U.S. In this time zone, Duke battles through horrors of new alien breeds in the future, and the zombified corpses of those who didn't survive the fallout. However, Duke in his fight, is teleported to the future, where the aliens have won and the humans are near extinction. Here, Duke discovers the aliens true plan, to go back in time, mess with historic events so Earth now wouldn't be what it is and make it so they could easily take over. Duke pummels the alien menace through the streets of New York with the help of some marines, and eventually gains access to the Statue of Liberty. Duke is called into action via the Government, aliens have once again landed and are wreaking havoc.
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