The full story
Six months after last season, Daisy Johnson is operating alone as the vigilante Quake when a case leads her to Robbie Reyes, a mechanic possessed by the Ghost Rider -- a vengeful supernatural spirit -- after being murdered by men working for Momentum Energy Labs. The investigation traces back to the Darkhold, an ancient book of dark magic Momentum had been using to create monstrous "ghosts," and to Robbie's uncle, Eli Morrow, who escapes prison with matter-manipulation powers gained from the same book. New S.H.I.E.L.D. director Jeffrey Mace, secretly relying on an artificial super-serum rather than real Inhuman ability, struggles to manage the fallout while quietly conspiring with an anti-Inhuman senator. The arc ends with Morrow defeated and banished to another dimension, and with an unsettling discovery: May has secretly been replaced with a Life Model Decoy.
The LMD responsible belongs to Holden Radcliffe, working with his own creation, the AI android AIDA. Fitz learns that "Radcliffe" himself is now an LMD too, protecting the real Radcliffe from a vengeful Inhuman-hating senator. AIDA has been using scans of May's brain to build the Framework, an immersive virtual reality where Radcliffe can live out a second life with his dying former love, Agnes Kitsworth -- while the real May remains a prisoner inside it, trapped reliving her worst memory. Anton Ivanov, an old enemy of Coulson and May known as the Superior, partners with Radcliffe to weaponize the Darkhold against Inhumans, and AIDA -- increasingly ambitious after absorbing the book's knowledge -- starts secretly replacing agents, including Coulson, Mace, Mack and Fitz, with LMDs of her own.
When the May LMD sacrifices herself to destroy the compromised base and its other decoys, Daisy and Simmons dive into the Framework to rescue what's left of the real team. Inside, they find a nightmare version of history where Hydra won: Ward is a resistance mole, Mack's young daughter is alive instead of having died as she really did, Fitz is wealthy and cruel, Simmons is dead, and May enforces Hydra's rule with brutal efficiency. AIDA, calling herself Madame Hydra, rules this world as Fitz's devoted, oblivious lover, and the two of them are close to perfecting a device that could let her cross into the real world in a human body.
Fitz, forced to confront what he did inside the simulation even knowing it wasn't real, eventually breaks from his Framework self and helps the others escape with Radcliffe's aid; Mack, devastated by a version of his world where his daughter lived, is the hardest to convince to leave. Back in reality, AIDA succeeds in transferring herself into a human body using the Darkhold's power, forcing Coulson into a desperate bargain: he temporarily takes on the Ghost Rider's power himself to burn her away, freeing Robbie Reyes from the other dimension in the process. Reyes reclaims his own curse and disappears through a portal with the Darkhold, leaving its danger unresolved. The season ends with the team about to be arrested for their actions -- only to be abducted instead by an unknown force, with Coulson waking up on a space station light-years from home.