星庭之战已经过去六个月，那场战役给霍金斯镇带来了灭顶之灾，自此以后人心惶惶。在想尽各种办法之后，我们这群朋友们首次各奔东西，他们努力应对复杂的高中生活，但这并没有让事情变得更容易。在这个最脆弱的时代，一个可怕的全新超自然威胁浮出水面，并抛出了一个可怕的谜题，如果能够解开这个谜题，就可能从彻底终结恐怖的颠倒世界。

该剧改编自作家罗伯特·麦卡蒙的小说《毒刺》，故事围绕乔治亚州农村的一群人展开，他们必须放下分歧才能在神秘的威胁中生存下来。

　　故事从两个不同寻常的“人类”开始，分别叫做George和Mitchell，他们一个是吸血鬼，一个是狼人，在当地一个不知名的医院里做苦工，他们生活绝望——因为mitchell是吸血鬼，George是狼人。他们决定改过自新，同住在了一起才发现，一个女鬼(Annie)死于神秘的情况并且经常闹鬼。不仅这样，Mitchell认识的几个吸血鬼和Mitchell不同，他们都对人类没有任何怜悯之心，而Mitchell不想这样，于是争端渐起。
　　三个非人住在一起，打算和人类和平共处，表现得更像是个人类，他们在这条看似不可能的路上到底要怎么走下去？让我们跟随三人的故事一同打开这个神秘世界的大门，通过他们看看我们的世界。by:yakubd.cc

　　故事从两个不同寻常的“人类”开始，分别叫做George和Mitchell，他们一个是吸血鬼，一个是狼人，在当地一个不知名的医院里做苦工，他们生活绝望——因为mitchell是吸血鬼，George是狼人。他们决定改过自新，同住在了一起才发现，一个女鬼(Annie)死于神秘的情况并且经常闹鬼。不仅这样，Mitchell认识的几个吸血鬼和Mitchell不同，他们都对人类没有任何怜悯之心，而Mitchell不想这样，于是争端渐起。
　　三个非人住在一起，打算和人类和平共处，表现得更像是个人类，他们在这条看似不可能的路上到底要怎么走下去？让我们跟随三人的故事一同打开这个神秘世界的大门，通过他们看看我们的世界。

　　Nina has been killed in a vampire attack and the gang now has to take care of baby Eve, whose werewolf heritage appears to have attracted the attention of vampire overlords known as the Old Ones. George dies while rescuing Eve, leaving her in the custody of Tom (who moves into Honolulu Heights) and Annie. Hal later turns up and becomes the new vampire at Honolulu Heights. Lawyer Nick Cutler, a vampire created by Hal in 1950, plans to expose werewolves as part of a larger plan involving a vampire conquest of Earth. Cutler tries to get Hal back to his old ways of drinking blood and eventually succeeds in breaking Hal down. The blood sends Hal into overdrive and he repulses Alex, whom he is dating, with his crude and unusual behaviour when they meet for a second date. Alex leaves angrily but is followed by one of Cutler's men. Meanwhile, Eve, from the future, reveals to Annie that in her future, most of humankind are dead or living in concentration camps and vampires now rule every inch of the world. Annie is shocked to learn that Hal is the ruthless leader of the new vampire revolution. To save the world, Eve asks Annie to kill her when she is a baby. Cutler reveals Alex's dead body drained of blood as revenge for Hal murdering his wife in similar fashion in 1950. Cutler then locks Hal up but Alex returns as a ghost and helps Hal escape. The Old Ones then arrive in Barry. To save the world Annie blows up Eve and The Old Ones, therefore saving the world, which is her unfinished business. The series ends with Hal, Alex and Tom living together in Honolulu Heights.

　　Disney+续订《鸡皮疙瘩》第二季，并将转为诗选剧的形式。

　　背景设定在一个平均水准酒店中的104号房间，剧集将讲述每集该房间的不同房客，他们形形色色的故事。