Some time after the events of the first Fusion Generation, former Indigo League Champion Ethan/Lyra dreams of an exciting new adventure. Encouraged by family and friends including Professor Elm, they set off to Cherrygrove City where Bill is about to unveil yet another invention to make a delivery that Elm says will aid victims of pickpocketing taking place in Kanto.
There they find rival turned friend Silver in a tense confrontation with his father Giovanni. They meet a Trainer named Dawn who introduces herself as the Champion of Sinnoh. Soon a flash of light blinds them and when it fades they find that a house has appeared out of nowhere.
Bill steps out of the house and explains that he's invented a Teleporter that will allow his cottage to travel across the world instantly. He offers to bring along the strongest Trainer in the crowd to a faraway island, and as Dawn and the player prepare to battle it out for the prize, they find that their Poké Balls have gone missing. Not only that but an angry mob forms saying that their Pokémon have disappeared from the PC.
Bill, Dawn, Silver, and Ethan/Lyra flee and nearby Giovanni plots to keep them away from the island. In Sea Cottage, Bill recalls the events of the original Fusion Generation and explains he's discovered wild Fusions on a remote island. He says that he developed the Teleporter and went to Cherrygrove City so that he could explore the island with a strong Trainer to accompany him. Now he fears that the same people responsible for fusing the island's Pokémon may be behind hacking PC storage systems around the world.
Before exploring the island, Bill offers Dawn, Silver, and the player the Fusions Cyndavee, Totovee, and Chikovee now that their other Pokémon including the player's Lugia have been taken. They step outside and find themselves on Splicen Island, a beautiful and apparently uninhabited location many miles off the coast of the Sinnoh region.
It's not long before Silver mysteriously vanishes, and the rest of the gang is left to search Splicen Island by themselves. They eventually stumble upon an abandoned laboratory where they hope to find Silver, but instead discover a PC containing all the stolen Pokémon, but now fused. They meet a mysterious boy who warns them to leave the island. Despite his efforts to stop them, Dawn recovers all the Pokémon on the PC and they are all returned to their original trainers.
With Fusions in the hands of more trainers than ever before, your character, Dawn, and other friends you meet along the way have to travel the world to unlock the mysteries of Splicen Island and find out who brought about another Fusion Generation and to what end.
Fusion Generation II includes all 104 of the original Fusions plus 336 new species for a total of 440. Many more of the Fusions in this entry can evolve, they can hatch from eggs, you can use Bill's machine to fuse your own, and the Time Capsule can be used to transfer Pokémon from the original Fusion Generation. Thanks to the inclusion of many more kinds of Fusions, starting with the second gym trainers use almost exclusively Fusions whereas in the previous game trainers using canon/unfused Pokémon was much more common.
The starter Fusions are once again based on Eevee but have three stages instead of two more like conventional starters, branching evolutions, and are received at the start of the game instead of being fused later. Additionally each can be taught to follow you around. Mareevee (Mareep + Eevee) is the counterpart to Pikavee from the first game being an electric type that evolves like the starters, but unlike Pikavee can't simply be obtained from Bill. Hogia, a fusion of Ho-oh and Lugia, appears on the title screen and Minusle, Minun and Plusle, as the game's icon.
Development of Fusion Generation II began in 2013 and ended in June 2014 due to legal threats from Nintendo of America. As indicated by her appearance at the end of the second game, a third featuring Hilda as the protagonist was to follow.