Andrew Garfield - Peter Parker/Spider-Man
Tom Hardy - Eddie Brock Jr/Venom
Ethan Hawke - Patrick Mulligan/Toxin
John Malkovich - Adrian Toomes/Vulture - Main Antagonist
Samuel L. Jackson - Nick Fury
Chris Zylka - Flash Thompson/Agent Venom
Laura Prepon - Silver Sablinova/Silver Sable
The film starts with the former Oscorp scientist Adrian Toomes examining a sample of the Carnage symbiote (which he retreaved from the aftermath of the final battle between Venom and Carnage) when it suddenly spawns a new symbiote and dies shortly after. Toomes then comes up with a plan to put this new symbiote under his control. Using Oscorp technology, he takes control of the symbiote. He then looks for a suitable host in New York and eventually finds an NYPD officer named Patrick Mulligan. To lure out Mulligan, Adrian Toomes uses experimental Flight technology to cause destruction thruogh New York. He is attacked by numerous NYPD officers and easily defeats all of them. He is eventually confronted by Patrick Mulligan who tries to shoot him, but Toomes disarms him and kidnapps him. Just as he escapes, Spider-Man arrives and asks some of the surviving NYPD officers what happened. After they explain this to him, Spider-Man tells them that he will stop him if he shows up again. Meanwhile, Eddie Brock is watching the news at his home and sees Toomes causing destruction throughout New York. He recognises him from somewhere and looks for an old photo of his father. He finds what he was looking for and sees a photo of his father, Richard Parker and Adrian Toomes. He researches Adrian Toomes and finds that he was a former Oscorp employee who got fired after he was caught trying to steal a project created by Oscorp only known as the suit. Apparently it was a cure for cancer but Adrian Toomes thought it could also be used as a weapon. Brock also finds that after Toomes was fired, numerous designs for Oscorp technology were stolen. Back at Toomes' lab, Toomes has Patrick strapped onto a table. When Patrick asks Toomes why he is doing this, Toomes says "I am doing this to gain power. The fools at Oscorp never did see the potential these symbiotic creations possessed. Luckily, I did." Toomes then injects Patrick with the new symbiote and takes control of him. Toomes then dubs this new symbiote Toxin. He then sends Toxin to attack the Oscorp building in New York to make all those who rideculed him suffer. Toxin then heads off to New York and attacks the Oscorp building. Spider-Man soon shows up and begins to battle this new threat. Toxin soon sends Spider-Man flying and prepares to finish him off, but NYPD officers show up and attack him. At Eddie Brock's home, he sees Toxin fighting the NYPD officers and recognises him as a symbiote and goes to stop him. Back at Oscorp, Spider-Man stops Toxin from killing any of the NYPD and gets Toxin to battle him again. They continue to fight through the Oscorp building until Toxin senses the Venom symbiote closing in and leaves. Spider-Man is then about to persue him, when he hears something behind him. He turns around to see another symbiote and at first thinks it is Harry Osborne, but soon relises that it isn't him. Venom then attacks Spider-Man, mistaking him for Toxin and Peter believes that Venom is an accomplise of Toxin. The two then have a brief fight, which is broken up when Toxin attacks both of them. The two then find out that they are on the same side and join forces to defeat Toxin. The two then battle Toxin through New York until Toomes contacts Toxin and orders him to retreat. Spider-Man then thanks Venom for his help and also tells him that he no longer needs his help. Venom disagrees with him and tells him that this is his problem now to. Meanwhile, Nick Fury follows Toxin back to Toome's lab and says "It looks like we're going to need some help." Fury then looks for a suitable canidate who is willing to use the small sample of the Venom symbiote that S.H.I.E.L.D. has left against Toxin. He eventually finds Flash Thompson who is willing to use the symbiote to help and becomes Agent Venom. Agent Venom and a group of S.H.I.E.L.D. agents are then sent into Toomes' lab to bring in Toxin. They soon encounter Toxin, who kills the S.H.I.E.L.D. agents. Agent Venom then battles him, but is easily beaten by this powerful symbiote. He is soon also attacked by Adrian Toomes, who is using the experimental flight technology to attack Flash. Flash is able to escape and informs Fury that the monster is known as Toxin and that he is under the control of a man named Adrian Toomes. After Flash tells Fury that he was unable to beat them, Fury decides to get Peter and Eddie's help. While Fury goes to get the help of Spider-Man and Venom, Toomes retreats to a secondary lab, off the shore of New York. Nick Fury then meets with Peter and Eddie and tells them about Toxin and how he is working for Adrian Toomes. Eddie knows that he worked for Oscorp, but Peter knows nothing about him. Fury then explains that he worked for Oscorp with Peter's fater and Eddie's father. He then tells them about the creation he tried to steal and reveals that it was actually the symbiote Eddie uses. Eddie and Peter tell him that they thought it was an alien life form and Fury reveals that S.H.I.E.L.D. only recently discovered that the symbiote is actually a living organic substance that was created to cure cancer, but went wrong, as Peter and Eddie's fathers found out that it could spawn other symbiotes and that it had developed a mind of it's own. So to keep it from endangering everyone it comes into contct with, Peter and Eddie's fathers sent it into space, but it eventually fell back to Earth by attaching itself to a comet that was heading for Earth, however, the comet broke in two when it was entering orbit and part of the symbiote was seperated from it's other half (Explaining how Eddie Brock and S.H.I.E.L.D. found two seperate symbiotes.) Peter and Eddie then agree to help stop Toomes and Toxin. Meanwhile, at Toomes' lab, Toomes contacts the mercenary Silver Sable and tells her that he will pay her a large sum of money to keep S.H.I.E.L.D. from interfearing with him and his work. He then has her keep S.H.I.E.L.D. away from him and his old lab (as it contains some of the research he was using to complete his ultimate goal which could reveal what he plans to do with Toxin.) Silver Sable first comes to Toomes' lab and collects her money and then heads off to keep S.H.I.E.L.D. away from Toomes' original lab. Nick Fury decides to have Peter, Eddie and Flash work together to stop Toxin and Toomes. He introduces Peter and Eddie to Agent Venom and Peter is shocked to find out that Flash now has a symbiote and is working for S.H.I.E.L.D. and Flash is shocked to find out that Peter is Spider-Man. After the introduction, the three head to Toomes' lab, but are unable to find him, however, they do find out what Toomes' plans to do with Toxin. Toomes' plans to forcibly spawn an army of symbiotes from the Toxin symbiote. As the three leave to inform Fury of this, a grenade suddenly lands behind them when they reach the exit of the lab. The grenade goes off and sends Peter, Eddie and Flash out of the front of the lab. It is then revealed that Silver Sable threw the grenade and is planning to stop them from reaching Fury. Flash tries to contact Fury, but he is attacked by two members of Silver Sable's mercenary group, the Wild Pack. As Peter and Flash fight off Wild Pack Merceneries, Eddie lunges at Silver Sable. The two battle until a Wild Pack mercenary shows up in a helicopter and attacks Eddie. Eddie then lunges at the helicopter and causes it to crash. The mercenary then tries to escape the wreck of the helicopter, but Eddie grabs him and sends him flying. Eddie then turns back to Silver Sable and begins figthing her again. Peter and Flash are able to defeat the Wild Pack and help Venom defeat Silver Sable. Flash then contacts Fury and S.H.I.E.L.D. takes Silver Sable prisoner. Nick Fury interogates her and she is willing to cooperate with him as long as she is given her freedom. Nick Fury tells her that she will be set free if she tells him where to find Toomes. She tells him and is set free. Nick Fury then sends Peter, Eddie and Flash to Toomes' second lab. Once they enter the lab, they encounter Toxin and battle him, however he is much to strong for them to beat. As Toxin is about to kill Peter, he kicks Toxin in the head and damages some of the technology controlling him. Patrick Mulligan begins to take some control of himself and tells Peter to get away from him and tells him that he is being controlled. Peter tells him to fight it, but Toomes takes control of him again and Toxin begins attacking him again. Peter then tells Eddie and Flash to hold Toxin still. The two then each grab Toxin by an arm and Peter begins punching him in the head in hopes of releasing Patrick from the control of Toomes. Patrick is released from the control of the Toxin symbiote and decides to help Peter, Eddie and Flash defeat Toomes. After getting through Toomes' range of security systems, they finally encounter him. The four then battle Toomes (who is using the flight technology), but are only able to beat him after Toxin unleashes his full power. Flash is then about to bring him in when Eddie attempts to kill Toomes, however, Peter and Patrick are able to convince him not to. Toomes is then put in a S.H.I.E.L.D. prison and all his equipment is retrieved from his lab. Fury then tells Peter, Eddie, Flash and Patrick that they did a good job, but is wondering what Eddie and Patrick are going to do. Eddie says "I might be leaving New York soon." Fury asks him if S.H.I.E.L.D. can count on him to help if their ever is another symbiote problem?" and Eddie says "If their is ever another symbiote problem, I will stop it." and then Peter says "You can count on me too Fury." Fury then asks Patrick what he is goin to do and he says "I can't get rid of this thing, so I'll use it for good, I'll use it to protect others." Eddie, Peter and Patrick then leave and Fury makes Flash a permenant S.H.I.E.L.D. agent and has him keep the symbiote.
In a post-credits scene, Nick Fury is called in to look a something Toomes made. A sort of super powerful symbiote fusion created from four different symbiotes.