- "It's a high-pitch frequency caused by Shockley's cellular vibration."
"The ramping up of his kinetic energy at an atomic level, and once it reaches a critical threshold, that massive energy transforms his body from a solid to a flammable gaseous state and then.."
- ―Leo Fitz, Jemma Simmons and Daisy Johnson
At the Playground, Jeffrey Mace learns from Jemma Simmons that the Patriot Serum that he has been using to pose as an Inhuman could endanger his health and that he must stop using it. Having to step away from the field, Mace still serves as the public face of S.H.I.E.L.D., arranging the relocation of Inhumans by the Watchdogs.
Indeed, the armed group is still very active and soon makes another victim: Anton Ivanov sends Tucker Shockley to expose Ellen Nadeer to a Terrigen Crystal since she could also be an Inhuman like her brother. However, it turns out that Nadeer is not an Inhuman, unlike Shockley, who undergoes Terrigenesis and uses is newly acquired explosive powers to kill the Senator and her staff. After S.H.I.E.L.D., unaware of Shockley's true nature, sends a team to investigate, Shockley is arrested and brought aboard the Zephyr One, that he nearly takes down before being ejected.
Another field mission is set up and successfully captures Shockley in a containment sphere designed by Leo Fitz, locking him in a secure containment sphere, but Mace is seized by the Watchdogs while ensuring the rest of the agents' escape.
Meanwhile, in Caldes de Montbui, Spain, Phil Coulson and Alphonso Mackenzie retrieve Agnes Kitsworth, Holden Radcliffe's former girlfriend. Though Radcliffe left her after failing to cure her of brain cancer, he never forgot Kitsworth since the Life-Model Decoy Aida was built with an exact resemblance to Kitsworth. Coulson and Mackenzie convince Kitsworth to arrange a meeting with Radcliffe so that S.H.I.E.L.D. could locate and rescue Melinda May.
However, Radcliffe, in turn, persuades Kitsworth that he has a way to save her: the Framework, a whole virtual rebuilding of the real world built by Aida thanks to the knowledge found in the Darkhold. Radcliffe, much to Coulson's dismay, takes Kitsworth with him and connects her body to the Framework. When her consciousness has successfully been downloaded in the Framework, Radcliffe euthanizes her body, wishing to ensure for her everlasting life in the virtual world.
- Clark Gregg as Phil Coulson
- Ming-Na Wen as Melinda May
- Chloe Bennet as Daisy Johnson/Quake
- Iain De Caestecker as Leo Fitz
- Elizabeth Henstridge as Jemma Simmons
- Henry Simmons as Alphonso Mackenzie
- John Hannah as Holden Radcliffe
- John Pyper-Ferguson as Tucker Shockley
- Parminder Nagra as Senator Ellen Nadeer
- Mallory Jansen as Aida / Agnes Kitsworth
- Zach McGowan as Anton Ivanov/Superior
- Jason O'Mara as Director Jeffrey Mace
- Max Osinski as Agent Davis
- Ricardo Walker as Agent Prince
- Deren Tadlock as Agent Cecilio
- Bryan Keith as Zach Bynum
- Sheila Cutchlow as Agent Jurmain
- Tom Virtue as Motel Clerk
- Tanner Gill as Driver
- Damian Gomez as Coffee Vendor
- Darsha Philips as Field Reporter
- Abraham Amkpa as Lab Tech
- Cherie Dvorak as Agent #1
- Pierce Minor as Watchdog #1
- Johnny Rivas as Waiter
- Caldes de Montbui, Spain
- Washington, D.C.
- Park Mesa Motel
- Calgary, Canada (mentioned)
- Los Angeles, California (mentioned)
- Majorca, Spain (mentioned)
- Attack on Ellen Nadeer
- Chase of Holden Radcliffe
- Kidnapping of Jeffrey Mace
- Assassination of Rosalind Price (indirectly mentioned)
- Attack on the Helicarrier (mentioned)
- Phil Coulson's Prosthetic Hand
- Terrigen Crystals
- Pick-Lock Devices
- Patriot Serum
- Patriot Suit
- Taser Rods
- Backscatter X-Ray Eye Implant
- Scepter (mentioned)
- Sokovia Accords (mentioned)
- Nitramene (mentioned)
- Humans First Movement (mentioned)
- Avengers (mentioned)
- United Nations (mentioned)
- Rosalind Price (indirectly)
- Grant Ward (indirectly)
- Glenn Talbot
- Steve Rogers
- Melinda May LMD
- Vijay Nadeer
- The explosion caused by Tucker Shockley that killed Ellen Nadeer and destroyed the Stamford Wing of Capitol Hill is a reference to the explosion caused by Nitro in Stamford in the comics, that ignited the Civil War.