Many months after their war with a rogue group of Inhumans, the team is still reeling. Coulson is again trying to put the pieces of his once revered organization back together while also dealing with the loss of his hand. His confidante and second in command, Agent Melinda May, has yet to return from an impromptu vacation with ex-husband Andrew; deadly superspy Agent Bobbi Morse is recovering from her traumatic torture at the hands of Grant Ward; Fitz is obsessed with discovering the truth behind the mysterious disappearance of Simmons; and all are on high-alert for the next move from Ward and Hydra.
When Coulson and the team discover a new Inhuman, S.H.I.E.L.D. comes face to face with another organization searching for powered people. And still reeling from Simmons' dramatic disappearance, Fitz goes to extreme lengths to try to learn how to get her back.
Fitz and the team enlist the aid of an Asgardian to unlock the secrets of the ancient monolith that swallowed Simmons, and Agent May is at a crossroads in her personal and professional life.
Daisy, Mack and Coulson race to protect Lincoln as Rosalind’s team hunts down the Inhuman in their quest for powered people. Meanwhile, Hunter proves that there is no line that he will not cross to exact his revenge against Ward and Hydra.
Having reluctantly agreed to share information with Rosalind Price and the ATCU, Coulson and the team go in search for the Inhuman who is killing off other Inhumans, and May feels that Hunter’s mission to take down Ward is getting too personal.
After her dramatic rescue from another planet, Simmons is still reeling from her ordeal and reveals how she had to fight for her life in a harsh new world.
The stakes get even higher as Hunter and May continue to go after Ward and Hydra, and Daisy and Coulson begin to suspect that the ATCU may be keeping a big secret from S.H.I.E.L.D.
As Daisy and the team fight to protect Inhumans, S.H.I.E.L.D. discovers the shocking truth about one of their biggest foes. Meanwhile, Fitz helps Simmons recover information that could lead them back through the portal.
The S.H.I.E.L.D. team discovers dangerous truths about the ATCU, and Ward’s plans to destroy S.H.I.E.L.D. takes a surprising twist.
Ward's campaign for revenge brings the S.H.I.E.L.D. team to their knees, and Coulson proves he will do anything to settle the score.
S.H.I.E.L.D. and Hydra go head-to-head in a battle that will change Coulson's world forever. While Daisy and her team of Inhumans fight to keep Hydra at bay, Coulson and Fitz take the ultimate risk.
In the aftermath of his trip to Maveth, Coulson is more determined than ever to get to Gideon Malick and put an end to Hydra once and for all. Daisy and the team encounter more Inhumans who have powers like they’ve never seen before, but will they be friends or enemies of S.H.I.E.L.D.?
Coulson and General Talbot are forced to team up and attend a worldwide symposium on Inhumans, where they suspect Malick has an inside man. As the S.H.I.E.L.D. team gets closer to the truth, an unexpected traitor is revealed.
Bobbi and Lance follow Gideon to Russia, and discover that he and a secret Inhuman are planning a coup. To stop them, the couple must make the ultimate sacrifice for the good of S.H.I.E.L.D.
Agent Mack and his brother step in when a radical group called the Watchdogs plans to eliminate the Inhumans; Simmons finds a powerful chemical compound.
The S.H.I.E.L.D. team tries to prove that fate is not fixed after Daisy is horrified by a glimpse of the future.
S.H.I.E.L.D. hunts for information on their dangerous new enemy, and a shameful secret from Malick’s past is exposed, threatening to destroy his Hydra legacy.
Agent Daisy Johnson brings the Secret Warriors together for a mission that will affect them all; knowledge of Hive's powers has S.H.I.E.L.D. mistrusting everyone.
The team reels from their losses as Hive continues to draw Inhumans to his side; Agents Fitz and Simmons get a lead that could stop the maniacal Inhuman forever.
Coulson and his team race to combat Hive’s control over the Inhumans, as their enemy’s deadly plan for the human race is revealed.
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. But with the stakes higher than ever and Hive growing stronger, the team is tested in ways they could never anticipate.
Hive's master plan is completely revealed, forcing S.H.I.E.L.D. into action.
Coulson and his team take on Hive before he can set off the warhead and transform the world's population into his Inhuman slaves. However, one team member will sacrifice themselves to stop the Inhuman leader.