SPIDER-MAN: NO WAY HOME features Doctor Strange (Benedict Cumberbatch) investigating why the dimensional barriers between parallel universes have been weakened, allowing beings from other universes to cross over into theirs, including six sinister supervillains that Spider-Man (Tom Holland) must deal with. This culminates in a post-credits encounter between Strange and the source of all the chaos: the Scarlet Witch (Elizabeth Olsen), who is now in posession of the Darkhold.

>DOCTOR STRANGE IN THE MULTIVERSE OF MADNESS reveals that the Scarlet Witch has been using the Darkhold to search the Multiverse for her twin sons Billy and Tommy, unaware that she is being manipulated by the cosmic abomination known as Shuma-Gorath so it can spread madness through the Multiverse. After an initial confrontation, she agrees to help Strange undo the damage she has inflicted upon reality by America Chavez (Xochitl Gomez), a young girl whose dimensional powers are pivotal to Shuma Gorath's plan. In exchange for her assistance, Strange vows to help her find the twins, but this effort leads to unexpected results.

>The growing Multiversal instability and its effects upon the timeline are first referenced in LOKI, which also reveals that the barriers of the Multiverse were broken once before, and it led to a "Multiversal war" which nearly destroyed all of creation in its wake and led to the creation of the Time Variance Authority.