Black Widow is certainly dead after the events of Rachel Weisz's Melina and O-T Fagbenle as Mason.
The much-anticipated film, which takes MCU's prime May release slot, will take fans back to the two years Avengers: Infinity War, allowing the movie's narrative without creating a plot hole considering Natasha's emotional death in Endgame. Despite this, many are still speculating that the standalone movie will eventually reveal the hero's not really gone, which Johansson effectively debunks.
While doing the promotional rounds for Taika Waititi's Jojo Rabbit, Johansson made a pit stop at The Tonight Show Starring Jimmy Fallon, where she expressed her excitement over Black Widow. She teased that it brought her closure following the character's death in Endgame, and added that while some people may still theorize Natasha is still alive somewhere, she's certain that she's really dead.
Honestly, it brought a closure to me that I needed, cause I was kind of wiped out after that last one [Avengers: Endgame] emotionally and literally... There are very few certain things but definitely, death is pretty certain. But, people definitely don't believe it and have tried to convince me that my character did not actually die. That may be, my character existed in an alternate universe. But no, death is a pretty final thing."
Johansson is referring to a few theories suggesting Widow didn't really die when she sacrificed herself on Vormir in exchange for the Soul Stone. This was actually discussed briefly in Endgame following her death when it was discussed if there was any chance they could revive her considering they had the Infinity Stones and a way to travel back in time. However, Clint Barton aka Hawkeye (Guardians of the Galaxy Vol. 3.
Whether or not Black Widow is truly dead, the fact of the matter is Marvel Studios can bring her back into the MCU if they want to. There's a number of ways they can resurrect a character, or even just use her in a creative way in future films, but that's something that they should be careful about. After Black Widow, it's best if they hold off using their deceased/retired heroes and focus on the active ones in the universe. Otherwise, it'll cheapen Avengers: Endgame's narrative.