Long ago, when Infinity War and the then-allegedly-untitled Avengers 4 were still in production, the Russos said that they could not reveal the official title of Avengers 4 yet because the title itself was a potential spoiler.
Hindsight being twenty-twenty, it's now pretty obvious what they meant. In the entirety of the MCU's history, the word 'endgame' has only been spoken twice. Once in Avengers: Age of Ultron when Tony, referring to the inevitable return of an alien threat, said;
"We're the Avengers. We can bust arms dealers all the livelong day, but that up there? That's the endgame."
Then the word was said more recently in Infinity War by Doctor Strange as he explained to Tony why he folded and gave Thanos the Time Stone, saying;
"We're in the endgame now."
Thus, the new title firmly supports the long-held theory that Doctor Strange may have purposefully done something to the Time Stone before he gave it to Thanos to help ensure they won in the long-run. Strange telling Tony "we're in the endgame now" now plays even more like it's him trying to tell Stark that this is the endgame he's always feared and that the only way to beat it starts with Strange giving up the Time Stone.
In other words, the entire plot of this new film may only be possible because of Doctor Strange's Time Stone-related back-up plan.