Charlie and Itchy are sent on a seemingly nefarious mission, unaware that who they believe is Annabelle is in fact her demonic cousin Belladonna.
Charlie needs a vacation, and manages to convince Itchy into taking one, but with so many bad things happening, Charlie can't even go a block without being someone's Guardian Angel.
Charlie and Itchy are assigned to return a cat named Dilly to her owner, but when Dilly gets taken in by a dog-hating cat lady, the duo must use a Miracle Dog Tag to become cats to rescue her.
A magic multiplying box spells three times the trouble when Charlie overbooks his afternoon between a date with Sasha, his poker buddies, and a fight with Otto and his gang.
Charlie volunteers to go get notes that David's crush Alex left in her mom's car, but Sasha must go with Charlie instead. Charlie, however, doesn't see women as good partners for this type of thing. Sasha decides to show Charlie what women can do.
Bess is being threatened by her ex Manfred and wants out to be with Itchy. Itchy tries everything to protect her but it's Charlie who saves Bess. Itchy is later hypnotized by a magician who turns him into a superhero.
Itchy is frightened by a wilderness movie, but Charlie tells Itchy that every dog has wolf blood in them, even Itchy. And so Charlie decides that they are going on a trip into the wild, so Itchy can live up to his heritage. They encounter a lost girl scout named Charlotte, and help her find her troop.
Charlie decides to try Kibbleland's new game, but he becomes selfish to not only think of himself and nobody else, not even Sasha. This becomes serious when Belladonna tricks Sasha into playing the game as a big tornado approaches and sucks her into the world of Kibbleland. The duo must find a way to rescue her before she's trapped forever.
Assigned to guard a crystal, Charlie and Itchy continue goofing off, but Charlie becomes convinced he's seen a UFO and Itchy doesn't believe him. The 'aliens', actually Carface and Killer, break into Charlie and Itchy's home and steal the crystal, prompting Charlie to get it back.
Itchy gets sent to the pound and has to break out with help from Killer.
Charlie has been lying a bit too much lately, so Anabelle makes his nose grow every time he tells a lie. Charlie must start telling the truth or face the consequences.
Charlie falls into a coma and has a dream of becoming a 1930s era detective to find out about a cat-scheme.
The next mission takes Charlie and Itchy to the sewers to help a colony of mice. Toxic smelling paint and other junk washed down the drains, taking away their freedom of living without worries. They join forces with Moxie, a mother mouse in the colony, to crack the case, and follow the drain to Carface and Killer's curio shop, where the villainous duo trying to transform new looking toy trains to look like antiques to sell for big money.