A critic for Next Generation commented that the game's graphics, audio, and gameplay 'are all on par' with Maximum Carnage, but that there was nothing new or interesting to set the game apart from its predecessor or the other beat 'em up games on the market. They generally regarded the ability to play as either Spider-Man or Venom to be the one good feature of the game. Reviewing the Genesis version, Electronic Gaming Monthly 's 'review crew' unanimously agreed that the game 'isn't much fun', particularly finding fault in the repetitive fights with the same enemies and the cheap combat, with its constant flow of unavoidable hits.

Confronting the five symbiotes at the Life Foundation Headquarters (as seen in Lethal Protector #5).

Spider-Man and Venom's escape from the Life Foundation (as seen in Lethal Protector #5).Removal of five symbiote seeds to create five new symbiotes (as seen in Lethal Protector #4).Appearance of The Jury (as seen in Lethal Protector #2).Discovering the underground city (as seen in Lethal Protector #1).Confronting the digger in San Francisco (as seen in Lethal Protector #1).Appearance of Spider-Man (in Lethal Protector #1).

The game's plot loosely follows Lethal Protector in the following ways: Though the game is titled after the comic book series Venom: Separation Anxiety, the story more closely follows the events of Venom's first limited series, Venom: Lethal Protector. The game received mediocre reviews, being criticized largely for its repetitiveness, unoriginality and lack of cutscenes. There is also cameo assistance from Captain America, Ghost Rider, Hawkeye, and Daredevil. The game boasts many thugs that the player has to defeat: heavily armed Jury and Venom's symbiote children. One or two players team up as Spider-Man and Venom to defeat the evil symbiote Carnage. Venom/Spider-Man: Separation Anxiety is a side-scrolling beat 'em up video game and a sequel to Spider-Man and Venom: Maximum Carnage, released for Mega Drive/Genesis and Super NES and then ported to PC.

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