- Guardians of the Galaxy
- Nocturnal (first appearance)
- El Diablo (first appearance) (flashback and main story) (origins revealed)
- Baxter Institute
- Mister Fantastic / Reed Richards (mentioned only)
- Dora Skirth
- Captain America / Steve Rogers (flashback and main story)
- Beast / Hank McCoy
- Jean Grey
- Wolverine / James “Logan” Howlett (flashback and main story)
- Venom / Eddie Brock (first appearance as Venom)
- Venom Symbiote
- Life Foundation
- Riot / Carlton Drake (single appearance as Riot; dies)
- Riot Symbiote (single appearance; dies)
- Riot / Carlton Drake (single appearance as Riot; dies)
- Kree Empire
- Korath the Pursuer
- Ronan the Accuser (mentioned only)
- Unnamed Sakaarians
- Scorpion / Mac Gargan
- Blizzard / Randy Macklin (first appearance)
- Pyro / Mark Raxton (first appearance)
- Spider-Man / Peter Parker (mentioned only)
In Life Foundation, Carlton Drake is overseeing the reconstruction of his destroyed laboratory while seeking out the surviving Symbiotes which were being experimented on. He eventually encounters the alpha Symbiote, Riot, which soon possesses him and urges him to find Venom as quickly as possible. Meanwhile, Life Foundation mercenaries are on the hunt for the fugitive symbiote until they are attacked and neutralized by Venom, who has found a new human host which matches him, and seeks mutual revenge on Drake.
In Pegasus Z, Captain America and Jean Grey are watching as Gamora is having some training with her childhood friend Nocturnal, an Inhuman with owl-like attributes and abilities, while Nathan Quill / Star-Lord is in Baxter Institute with Dr. Hank McCoy / Beast and Dora Skirth experimenting on the Anti-Venom, a new type of synthetic symbiote created to extinguish other symbiotes, as a means of preparation for the possibility of a Symbiote pandemic. Nearby, Groot, Nebula, Rocket Raccoon, Drax the Destroyer, Cougar and Yondu Udonta are battling a Kree squad led by Korath the Pursuer, who is attempting to access Baxter Institute's teleportation terminals to enter Pegasus Z. Just then, Korath is attacked by Venom, who greatly injures him and forces him and his squad to retreat. Venom soon reveals his new host to be Eddie Brock, a disgraced, former Daily Globe journalist who was fired for ranting on Drake and his Life Foundation experiments and allegations without any sources. The Guardians and the others regroup at McCoy's lab, where they view Brock's log about Drake's secret experiments, on which he used both prison convicts and homeless people who did not survive the progress. The Guardians reluctantly agree to team up with Venom to stop Drake, while also advised by Captain America to be prepared in case he steps out of line, and Skirth keeps the Anti-Venom hidden in her desk to avoid Venom's misunderstanding. Unbeknownst to her, the Anti-Venom also has a consciousness of its own.
Through a communicator Skirth implanted in one of Drake's security guards before she left, the group overhears that Drake is hiring some of the supervillains (Scorpion, Blizzard and Pyro) incarcerated in the Raft to hunt down Venom in exchange of reducing their prison sentences. Star-Lord and Gamora record his conversation while planning to deliver them to the authorities. The group spilts up, with some infiltrating Life Foundation to find out more abut Drake's plans while others go with Venom distract the villains. Jean, Gamora, Drax, Rocket, Nebula and Beast infiltrate Drake's hidden lab and discover that the scientist are also experimenting on El Diablo, an altered, highly intelligent red Tyrannosaurus Rex from World War II who has been in suspended animation for decades. Star-Lord, Captain America, Wolverine, Groot, and Venom defeat the bounty hunters and are contacted by Gamora about El Diablo. They make it into Life Foundation, but are confronted by Drake, who takes the form of Riot and attacks them. Skirth soon has Nocturnal take her and the Anti-Venom to the area, where she reluctantly uses the Anti-Venom on herself.
Just as Skirth joins the fight, Venom (presuming that the heroes plan to terminate him as well) takes control and begins attacking both the heroes and Riot, although he is unable to attack the Anti-Venom, which is shown to be toxic to the other Symbiotes. Star-Lord reaches Gamora's group and conjures numerous heat blasts to unfreeze El Diablo and Rocket broadcasts the evidences of Drake's crimes to the Daily Globe, and El Diablo absorbs the Kree and Chitauri technology stored in the facility (creating a new armor for himself) before destroying the facility and the experiments in it. The Anti-Venom suit soon begins taking control of Skirth's until Star-Lord and Nocturnal free her, leaving the Anti-Venom to attack Venom and Riot on its own. Venom lures Riot and Anti-Venom into a rocket and programs it to take off. The then traps the two in it and damages the probe as it takes off, causing it to explode and kill both Riot and Drake and destroy the Anti-Venom while Venom disappears in the nearby ocean. As Skirth is given medical attention and cleared out of her assignment in Life Foundation by Reed Richards, El Diablo makes a new home for himself in Pegasus Z as Gamora continues training with Nocturnal. While unsure of Venom's whereabouts, Star-Lord and Beast are certain that other Symbiotes may be coming, and work to be prepared for their next move. Meanwhile, Brock and Venom have relocated in San Francisco, and resume their hunt for criminals.
- Scott Menville as Star-Lord / Nathan Quill
- Laura Bailey as Gamora / Zoe Gillan
- Troy Baker as Rocket Raccoon / Sebastian Allan
- Travis Willingham as Groot, Beast / Dr. Hank McCoy
- Erica Lindbeck as Nebula, Jean Grey
- Yuri Lowenthal as Nocturnal
- William Salyers as Yondu Udonta
- Roger Craig Smith as Captain America / Steve Rogers
- Danica McKellar as Dora Skirth
- Steve Blum as Wolverine / James “Logan” Howlett, El Diablo, Riot
- Crispin Freeman as Venom / Eddie Brock
- Kevin Michael Richardson as the Venom Symbiote
- Benjamin Diskin as Carlton Drake, Sakaarian Captain
- Dave Fennoy as Korath the Pursuer
- Liam O'Brien as Scorpion / Mac Gargan, Pyro / Mark Raxton
- Dee Bradley Baker as Blizzard / Randy Macklin, Sakaarian scout
- The episode is entitled after the 2006 song "Back to Black" by Amy Winehouse.
- It also shared the same title of a episode in Ultimate Spider-Man, which also featured Venom as an antagonist.
- "St. Elmo's Fire (Man in Motion)" by John Parr