Noticing a change in little bro Danny since the accident in the lab, Jazz mistakes his ghost hunting for depression and signs him up for therapy with Penelope Spectra, not knowing that Spectra is a ghost who feeds off teen misery!

After being bitten by tiny green ghost beetles, the kids of Casper High get a mysterious illness that gives them ghost powers and are quarantined at a spooky old hospital outside of town. When Danny sneaks into the hospital to investigate, he is captured by Penelope Spectra and her assistant, Bertrand. They are the ones who started this illness as part of their plan to build Penelope a young and beautiful new body. All she needs is Danny's half-human/half-ghost DNA to complete her ghostly plan. With Danny captured and Sam sick, it's up to Tucker to conquer his fear of hospitals and free Danny before Penelope gets what she's after.

After an argument with their respective boyfriends, Spectra, Kitty and Ember join forces and use their powers to make all men vanish. Danny and Jack are fishing in Lake Eerie, the only place on Earth immune to the spell. Sam, Jazz and Maddie must stop the villainesses while Danny is out of town. Unfortuantely for Danny, Skulker is taking more time hunting Danny to prove his girlfriend how great hunter he is. Can Amity Park be saved without its hero?