My take from this:
1.) This is Post-Loki.
2.) First part of the movie is Wade adjusting to his new life after saving Vanessa from being killed. He's retired from being an assassin, as you see in the trailer where he's working as tech support at a small company, looking at his old costume in his work locker; longing for his old 'career' back. He has a heart to heart with Vanessa about this and ultimately is talked out of being an assassin again and finally Wade is at peace with himself. On his birthday, the TVA show up to apprehend him as his temporal aura is misplaced - but they also use the opportunity to hire him (his regenerative factor is useful?) as an assassin to do one simple task on the Sacred Timeline - with the promise that he'll be sent home.
3.) The Nexus Event that Deadpool is hired to prevent in the Sacred Timeline involves something in Europe or Asia - perhaps to do with Wolverine. He finds the fake Wolverine in the Casino (seen in the trailer) played by Daniel Radcliffe. His character (an escaped shape-shifting mutant prisoner of the TVA - I guess
Kevin Sidney?) isn't supposed to be on the Sacred Timeline and working for an underground group of Mutants in The Void lead by Cassandra Nova Xavier. (More on that shortly.)
4.) Wade eventually kills the poor shape-shifter - but soon discovers that the TVA was never going to send him home and would have pruned him out of necessity after the job was done. By removing this time-displaced Wade from the universe his existence/aura was anchored to, where he undid Vanessa's death and finally lived a happy life, it is revealed that reality is now destroyed due to his removal from that timeline. Meaning, everyone and everything he loved is gone. Erased from existence. (This isn't Earth-17315 - the Logan future - as more is revealed.)
5.) Wade, grief-stricken by this loss, starts killing TVA agents in a fit of fury before he's eventually overpowered and pruned - taken to the Void. There, he discovers a Wolverine variant (Hugh Jackman in his comic suit and all) who is actually from the Sacred Timeline - and wasn't meant to get pruned (due to something that involved Cassandra Nova Xavier as well) but did anyways, creating a domino effect leading to no X-Men on Earth-199999. Wolverine became aware of this during his time in the Void.
6.) The duo team up to look for Cassandra. As it turns out, Wade Wilson was lured out of his timeline by Daniel Radcliffe's character who escaped thanks to Cassandra's extremely powerful interdimensional/telepathic abilities, and TVA wouldn't have apprehended Wade in the first place and would let him live his own happy life on his branch if not for her. Since only one of her existed in a multitude of timelines, Cassandra's goal is to rid all of Xavier's legacy through-out the multiverse as revenge for never having a chance to exist on her branch which was pruned before the events of Loki. (Maybe some implication that Mutants were doomed no matter the timeline - Earth-10005, Earth-17315, Deadpool's timeline post-DoFP, etc even the Sacred Timeline - thanks to her staging some event.)
7.) Eventually Wade and Wolverine kill her and all her Mutant variant lackeys, and...from there, I don't know how to theorize how it goes from here but Deadpool somehow ends up out of the Void and maybe Wolverine dies, I dunno. Anything's possible.
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