The game is based loosely on a mini-series of comics about the Venom saga.
Despite the title of Separation Anxiety, the game mostly consists of the story comprising Venom's Lethal Protector mini-series.Separation Anxiety is a 2D side-scrolling platform-action beat 'em up game featuring several prominent characters from the Marvel Universe and gripping storylines taken from the popular Spider-Man comics. The player/players travel through 18 levels until the Life Foundation's plans are utterly foiled. Spider-Man and Venom team up against the new threat of the Life Foundation, and their five newly spawned symbiotes: Having escaped from the clutches of the treacherous Life Foundation, Venom seeks the aid of his most hated foe, Spider-Man! A tenuous alliance is formed as the Lethal Protector and the Amazing Web-Slinger race to stop the life Foundation from using the symbiotes spawned by Venom in their evil undertakings. Digger (First and only known appearance). Captain America's Uniform and Shield (Last appearance). The Scream Symbiote (First and only known appearance). The Agony Symbiote (First and only known appearance). The Lasher Symbiote (First and only known appearance). The Phage Symbiote (First and only known appearance). The Riot Symbiote (First and only known appearance). Spider-Man's Suit and Web-Shooters (Last appearance). Daredevil (Matt Murdock) (First and only known appearance). 
Hawkeye (Clint Barton) (First and only known appearance). 
Ghost Rider (Johnny Blaze) (First and only known appearance). Captain America (Steve Rogers) (Last appearance). Some other heroes and anti-heroes aid Venom and Spidey throughout the game, making brief cameos to attack the player's foes. Carnage (Cletus Kasady) (Final surprise boss) (Last appearance). Scream (Donna Diego) (First and only known appearance). Agony (Leslie Gesneria) (First and only known appearance). Lasher (Ramon Hernandez) (First and only known appearance). Phage (Carl Mach) (First and only known appearance). Riot (Trevor Cole) (First and only known appearance). Life Foundation Symbiotes (First and only known appearance). Wysper (Jennifer Stewart} (First and only known appearance). 
Firearm (First and only known appearance). Bomblast (First and only known appearance). Screech (Maxwell Taylor) (First and only known appearance). Ramshot (Samuel Caulkin) (First and only known appearance). 
Sentry (Curtis Elkins) (First and only known appearance).The Jury (First and only known appearance).Spider-Man (Peter Parker) (Last appearance).
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