Alex, Marty, Melman, Gloria, Zuba and Florrie (along with Kronk, The Penguins of Madagascar, King Julien, Maurice, Mort, Terk, Tantor, Louis, Sebastian, Baloo, Bagheera, King Louie, Fu Dog, Rutt and Tuke, Roger Rabbit and Lucky Jack) have come back to Heaven, new home of Charlie Barkin and Itchy Itchiford. During their visit, Gabriel's Horn is stolen by Carface. They go back to the real world and land in San Francisco, California. During their time on here, they meet a beautiful Irish Setter named Sasha La Fleur, whom Charlie falls in love with. They also meet Sasha's owner, David. Together, they must search the city for the Horn and stop a demonic Hellcat named Red (whom Shere Khan, Yzma, Fat Cat, and Makunga work for) from getting his paws on it.
- Kronk, The Penguins of Madagascar (Skipper, Kowalski, Rico, and Private), King Julien, Maurice, Mort, Terk, Tantor, Louis, Sebastian, Baloo, Bagheera, King Louie, Fu Dog, Rutt and Tuke, Roger Rabbit, Lucky Jack, Shere Khan, Yzma, Fat Cat, and Makunga guest star in this film.
- This film will be dedicated to the memory of Ernest Borgnine, who first replaced Vic Tayback as the voice of Carface Cruthers in the real film, due to his death on July 8, 2012.
- Jonathan Oosterhof (aka LionKingRulezAgain1) originally planned to make a Lion King crossover with All Dogs Go to Heaven 2 with the entire Jungle Adventure Crew joining and Lucky Jack and Fat Cat as guest stars, but he retired from making anymore crossovers, so most of the Jungle Adventure Crew ended up guest starring in this film instead.
- The only reason why Kronk is in this film is because Zazu is the only member of Daniel Esposito's Pooh's Adventures team to guest star in Littlefoot's Adventures of All Dogs Go to Heaven 2 and The Vultures and Jiminy Cricket will guest star in Aladar's Adventures of All Dogs Go to Heaven 2.
- The storyline continues in Alex's Adventures of All Dogs Go to Heaven: The Series and Alex's Adventures of An All Dogs Christmas Carol.
- Like SuperKitaroShinX's original version of Pooh's Adventures of All Dogs Go to Heaven 2, this is an NTSC film with NTSC bits from the Madagascar films, The Emperor's New Groove, Kronk's New Groove, the Tarzan films, The Princess and the Frog, The Little Mermaid films, Brother Bear 1 and 2, The Jungle Book, TaleSpin: Plunder and Lightning, Who Framed Roger Rabbit, and Home on the Range.