[SPOILERS for Agents of S.H.I.E.L.D. season 3 ahead.]
ABC/Marvel's Agents of S.H.I.E.L.D. essentially went through a partial reboot during its first season when Captain America: The Winter Soldier was released in theaters - as the Marvel Cinematic Universe's version of the S.H.I.E.L.D. organization was officially dissolved and had to take the ongoing battle with Hydra underground. S.H.I.E.LD. season 2 was already well into its own Inhumans-centered storyline by the time Avengers: Age of Ultron hit theaters in 2015, but the show still featured a firm connection to that film all the same (even though Age of Ultron's corresponding impact on season 2 was minimal, like the effect that Thor: The Dark World had on season 1).
Seeing as Agents of S.H.I.E.L.D. season 3 has, to no small degree, dealt with the idea that more and more Inhumans are now running around the MCU version of Earth, it's long been presumed that the ABC TV show will similarly tie into the events of Captain America: Civil War - in which newly-proposed legislature requires people with super-powers and/or "special abilities" around the world to register with their governments. Said tie-in will be occurring soon, what with Civil War opening in U.S. theaters just before S.H.I.E.L.D. season 3's penultimate episode (and then its two-part finale).
The newly-unveiled official synopsis for S.H.I.E.L.D. season 3's penultimate episode offers a sneak peek at how, exactly, those "Sokovian Accords" (as they're known) in Civil War affects Director Coulson (Clark Gregg), his agents, and the Inhumans of the MCU. You can read the synopsis for that episode (titled "Emancipation"), below:
With only two episodes left before S.H.I.E.L.D. loses one of their own, Daisy’s prophecy ticks closer towards a major loss, as the aftermath of the events of “Marvel’s Captain America: Civil War” force S.H.I.E.L.D. to register the Inhumans, on “Marvel’s Agents of S.H.I.E.L.D.,” TUESDAY, MAY 10 (9:00-10:00 p.m. EDT), on the ABC Television Network.
The Inhuman Hive, having taken over the dead body of ex-S.H.I.E.L.D. agent (and Hydra leader) Grant Ward (Brett Dalton), has now started to assemble his own group of "followers" - that is, fellow Inhumans whom he has infected and taken control of using his parasitic abilities with the end goal of creating a new world order - on the latest Agents of S.H.I.E.L.D. episodes. The last two season 3 episodes in particular ("The Team" and 'The Singularity") further revealed that is it near-impossible to tell whether an Inhuman has been infected by Hive until they so decide to show their hand.
As such, it's not too surprising that Couldson and S.H.I.E.L.D.'s short-term solution to their Inhuman-related problems is to go along with the demands of government officials who want super-powered individuals registered - and in turn, keep stricter tabs on the Inhuman members of the general population, at least until they have the Hive situation under control. What will come after that for the humans and Inhumans of Earth in the MCU alike, well, that's what Agents of S.H.I.E.L.D. season 4 is going to be about. It's possible that Hive will serve as the main antagonist at the beginning of season 4 too, should his story thread not be resolved over the course of the season 3 two-part finale, "Forgiven" and "Ascension" (not that we would complain about that, per se).
Of course, a very important part of the problem with Hive - as far as Coulson and his agent 'family' are concerned - is that he now controls Daisy (Chloe Bennett), not too long after the latter had a vision of someone's death; a vision that Agents of S.H.I.E.L.D.'s viewers have likewise gotten a good look at themselves, over the course of season 3's second half. IGN debuted the above artwork for the remaining four episodes of S.H.I.E.L.D. season 3 (a.k.a. part of the show's "Fallen Agent" story arc), which calls further attention to the matter of Daisy's vision by paying homage to the cover for The Amazing Spider-Man comic book issue #131: the cover that alluded to the infamous death of Gwen Stacy, even as it also suggested any one of Spider-Man/Peter Parker's close acquaintances was fair game for the chopping block.
The question isn't necessarily whether or not an important character will, for sure, die on Agents of S.H.I.E.L.D. before season 3 draws to a close; rather, it's a matter of whether or not that character will die and stay dead. Coulson himself famously "recovered" from being dead, while the S.H.I.E.L.D. TV show's writers/producers found a way to keep Dalton in the mix even after his original character Ward was killed. On the other hand, important S.H.I.E.L.D. characters have suffered permanent deaths at this stage too (R.I.P. Antoine "Trip" Triplett), so we may yet have to bid a proper farewell to someone else on the show before season 3 draws to a close.
Agents of S.H.I.E.L.D. season 3 continues with ‘Failed Experiments’ Tuesday, May 3rd at 9pm on ABC.