The English filmmaker will step back into a producer role, with Bryan Singer now regarded as 20th Century Fox's top choice to helm the X-Men: First Class sequel, according to Deadline.
The publication claims that Vaughn will produce the upcoming film alongside Simon Kinberg and Lauren Shuler Donner.
He will also likely direct another Fox picture, Secret Service - an adaptation of the Mark Millar comic book series.
Singer oversaw the first two X-Men feature films in 2000 and 2003, and worked as a writer and producer on First Class.
Stars Michael Fassbender, James McAvoy and Jennifer Lawrence have all been confirmed for First Class sequel Days of Future Past.
> Mark Millar: 'X-Men: Days of Future Past is X-Men meets Terminator'
> Patrick Stewart hints at 'X-Men' return
> James McAvoy wants two more 'X-Men' films
Watch Jason Flemyng discuss X-Men: Days of Future Past with Digital Spy below: