Agents of S.H.I.E.L.D. season 6 will completely ignore both the snap and the events of Avengers: Endgame. When Agents of S.H.I.E.L.D. launched in 2013, it was the official tie-in TV show, and the first season was particularly loved because of its stunning tie-in to Captain America: The Winter Soldier.
Over the years, as Marvel Television and Marvel Studios have become more distant, the tie-ins have been rarer - and have usually been thematic, such as with the inclusion of Ghost Rider in Agents of S.H.I.E.L.D. season 4, timed to coincide with the introduction of magic to the MCU in Doctor Strange. But season 5 moved a lot closer to the movies, revealing that Hydra had formed an alliance with an alien Confederacy because they believed Thanos was destined to return. The final few episodes even included TV footage of the Black Order's attack on New York, and commented on Tony Stark's disappearance. But, to the surprise of viewers, the show completely ignored the snap.
In an interview with The Wrap, Marvel TV chief Jeph Loeb confirmed that this will continue to be the case; neither the snap itself, nor the events of Avengers: Endgame, will be referenced. It's because Marvel Television had absolutely no idea what was going to happen in Avengers: Endgame. They didn't know what the world would look like post-snap. What's more, while they knew a fair amount about the plot, they didn't know for sure when their show would air, and as a result they were wary of unwittingly spoiling something. As Loeb explained:
"We don’t want to ever do something in our show which contradicts what’s happening in the movies. The movies are the lead dog. They’re setting the timeline for the MCU and what’s going on. Our job is to navigate within that world. The only way for us to tell our story is to do them pre-snap. Whether or not you can figure out [how the timeline works], we’ll let 'timelords' figure out."
On the face of it, there is quite simply no way to "figure out" how to reconcile the timeline. Agents of S.H.I.E.L.D. season 5 ended during the first stages of Avengers: Infinity War, with Thanos' forces beginning their attack upon the planet. At WonderCon, Marvel Television confirmed that season 6 is set a year later, which means it should really be partway through the Decimation era - but it's not. Therefore, Agents of S.H.I.E.L.D. can no longer be considered part of the same shared universe as Avengers: Infinity War and Avengers: Endgame. The MCU's official tie-in TV series is not tying into the biggest event in the history of the MCU.
There is only one possible in-universe explanation for this. Agents of S.H.I.E.L.D. season 5 used time travel, with the S.H.I.E.L.D. team transported to a dystopian future in which the Earth had been destroyed. They then traveled back to the present in order to avert the planet's destruction. Given the logic of time travel in Avengers: Endgame, it's possible they unwittingly created a separate branch of reality when they did this. This timeline could be one beyond the 14,000,605 that Doctor Strange viewed; one in which Thanos was actually defeated at Wakanda. But if that is the reason, Marvel Television will really need to explain it sooner rather than later, and frankly that risks undermining the drama of Avengers: Endgame - because there presumably was another way after all.
Co-showrunner Jed Whedon said, "We have a logic in our head that makes sense. But we certainly don’t want to burden the audience of telling them all that. We just want them to enjoy the ride and let the couch discussions be about that." It remains to be seen whether or not that proves to be a wise decision.
Source: The Wrap