S.H.I.E.L.D. puts everything on the line to survive a war that blurs the line between friend and foe. Coulson and his team will be forced to make shocking sacrifices that will leave their relationships and their world changed forever.
At the Playground, Phil Coulson reinforces the S.H.I.E.L.D. SUV with an Electronic Battering Ram in order to hold the super-strong Calvin Zabo, pinned against the wall. Coulson talks with Zabo and tells him that he wants the best for Skye, too. He helps Zabo realize that Jiaying is the one acting as a monster, not the good-hearted Zabo, and protecting Skye includes protecting her from her own mother. Zabo finally agrees to help Coulson and his team to stop Jiaying.
Meanwhile, Melinda May, Lance Hunter, and other S.H.I.E.L.D. agents enter the building where Bobbi Morse is held hostage; they are oblivious to the trap set by Grant Ward where if anyone enters the room holding Bobbi Morse, he will be killed. Kara Palamas manages to kill one of the S.H.I.E.L.D. agents and steals his radio. After Palamas and May exchange gunfire, May devises a plan to defeat Ward and Palamas. She tells the agents to meet using the radio, but not to drop their guard unless they see May's face. Palamas, overhearing the call, uses the Photostatic Veil to put on her "May" disguise to meet the agents. Ward runs into Palamas, disguised as "May" and immediately shoots her several times before realizing whom he just killed. Hunter finds Morse's room, opening the door to have Morse save his life by leaning in front of the gun and taking the bullet in her shoulder. May and Hunter rush back to the Playground with the critically injured Morse while Ward escapes.
As the Inhumans proceed to attack the Iliad, by grouping and holding hostage all agents, Skye is locked up with power-canceling restraints on her arms. Alphonso Mackenzie, who stayed back on the ship after finding out that Robert Gonzales was dead, finds Skye and rescues her so that they can defend the ship together. Jiaying plans to use the Terrigen Crystals to transform (or simply kill) as many S.H.I.E.L.D. agents as possible. She uses a Crystal to kill Oliver so that Anne Weaver would expand the S.O.S. beacon to call all of S.H.I.E.L.D. to help the Iliad. Mackenzie and Skye watch the demonstration from a hacked feed and determine that they must end the hardwired distress call.
Seeing Morse's injuries and the affection Hunter demonstrated cause others to think of their loved ones. May calls Andrew Garner and tells him that she wanted to hear his voice. Jemma Simmons finds Leo Fitz alone, prepping for his mission on the Iliad, and tells him that they needed to talk about how she feels about him.
Coulson and his team arrive on the ship, after telling all other Quinjets to hold back; they had received a message from Skye, telling them that it was a trap. Zabo tells Coulson that he will deal with his wife, while Coulson deals with the modified Terrigen Crystals. Though May disagrees with the plan, all depart.
Skye is fighting Alisha Whitley and her duplicates when Lincoln Campbell and May arrive to assist her. As Skye leaves to find Jiaying, May and Campbell continue the fight. When May aims to kill the real Whitley, Campbell stops her, citing that the Inhumans have been misled, but are not evil, before electrocuting Whitley.
Coulson, Mackenzie, and Fitz find the Terrigen Crystals in the ventilation room, and Fitz busies himself with setting up a trap using Quantum Field Disruptors that will prevent Gordon from teleporting out of the room. When Gordon teleports in, a fight begins, with Coulson armed with a giant wrench, Mackenzie with a fire ax, and Fitz with a pipe against Gordon's limited teleporting powers, as gunfire would ricochet in the small room. Fitz lands the killing blow accidentally when Gordon teleports, solidifying impaled by the pipe. The Terrigen Crystal in Gordon's hand falls and Coulson catches it. His arm slowly turns to stone before Mackenzie chops off his hand to prevent the corruption from spreading to the rest of Coulson's body.
Skye finds Jiaying on the ship's deck and confronts her. Jiaying is willing to kill her own daughter, saying that destroying humanity is her greatest gift to this world, not Skye. Skye blasts the Quinjet carrying the modified crystals into the ocean. Jiaying grabs Skye and begins to absorb her energy; Skye grabs Jiaying and begins to use her vibrational power. Zabo comes, telling Skye that he will bear the burden, and kills Jiaying with his super strength.
At the ocean's bottom, the Terrigen Crystals interact with the wildlife. The fish are caught by fishermen and eventually turned into fish oil pills that are distributed in stores worldwide.
Zabo undergoes the T.A.H.I.T.I. Protocol, losing his memories and the burden of killing his wife, and becoming a veterinarian. Coulson, missing a hand, and Skye start a superpowered faction of S.H.I.E.L.D. called the Caterpillars. May takes time off from S.H.I.E.L.D to make amends with Andrew Garner. Morse tells Hunter that she no longer wants to be in S.H.I.E.L.D. Ward becomes the new leader of HYDRA. Fitz and Simmons' newfound relationship is cut short when Simmons is sucked into the mysterious Monolith because Fitz accidentally opened the box.
- Clark Gregg as Phil Coulson
- Ming-Na Wen as Melinda May and Agent 33
- Brett Dalton as Grant Ward
- Chloe Bennet as Skye
- Iain De Caestecker as Leo Fitz
- Elizabeth Henstridge as Jemma Simmons
- Nick Blood as Lance Hunter
- Adrianne Palicki as Bobbi Morse
- Kyle MacLachlan as Calvin Zabo
- Henry Simmons as Alphonso Mackenzie
- Dichen Lachman as Jiaying
- Jamie Harris as Gordon
- Maya Stojan as Kara Palamas/Agent 33
- Luke Mitchell as Lincoln Campbell
- Christine Adams as Agent Anne Weaver
- Mark Allan Stewart as Agent Oliver
- Blair Underwood as Andrew Garner
- Alicia Vela-Bailey as Alisha Whitley
- Brendan Wayne as Jiaying's Assistant
- Daz Crawford as Kebo
- Robert Reinis as Bartender
- Loki as Thug #2
- Anthony D. Washington as TAC agent #3
- Damien Coates as Inhuman (uncredited)
- Kidnapping of Bobbi Morse
- War against the Inhumans
- Massacre in Hunan (mentioned)
- Terrigen Crystals
- Terrigen Mist
- Photostatic Veil
- Quantum Field Disruptors
- Bulletproof Vest
- Nature Max Supplements Fish Oil
- Electronic Battering Ram
- Caterpillars (mentioned)
- Strategic Scientific Reserve (logo)
- Avengers (mentioned)
- Fox News (mentioned)
- This episode originally aired alongside S.O.S. Part One as part of a two-hour finale.