The game takes place alongside the events of the second season of the Transformers: Prime cartoon, and involves the Autobots and Decepticons battling over a mysterious meteor made of Dark Energon and its legendary contents.
The Decepticons have discovered a gigantic asteroid composed entirely of Dark Energon, and the Nemesis has traveled into Earth's orbit to obtain it. Once the Autobots became aware of this development, Ratchet sends Optimus Prime, Arcee, Bumblebee, and Bulkhead onto the surface of the Nemesis via GroundBridge to stop them.
As the other Autobots take care of incoming Vehicon Jets, Optimus fights his way along the Nemesis deck to the machinery tethering the asteroid. He quickly destroys the generator and the asteroid lags behind... until the Decepticon ship fires three more tethers from underneath. Unable to get a good firing angle on the tethers, the four Autobots leap to the rock in vehicle mode. Facing down a few more Vehicon Jets, Optimus destroys all three tethers quickly using a vehicle mode ramming attack, but finds himself facing down Megatron. The vehicle-ram move breaks through Megatron's defenses, and by charging up his energy, his upgraded attacks send Megatron reeling.
Just as Optimus gain the upper hand, the asteroid begins to crumble. As Optimus stares into a deep fissure opening at his feet, two yellow dots look back... and the asteroid shatters, its pieces, and the Autobots, plummeting to Earth. Starscream gloats, mocking their inability to fly, but Megatron quickly rebukes him, demanding his minions hunt down both the Autobots to make certain they perished in the fall, as well as recover as many of the meteorites as possible.
- Despite being around the time of Season 2 according to a producer at Activision, it is currently unknown why Smokescreen or Wheeljack were not in the game.
- At BotCon 2012, concept art for a Tank Vehicon and a Helicopter Vehicon was released.
- Unlike other Transformers games, the differences in the versions of Prime - The Game mostly involve presentation, not story.
- As there is a playable segment where you control Jack and Arcee in her bike mode, this could possibly be considered the first game to have a playable human. It's most likely Arcee, though, considering Jack was carrying a huge cylinder and lacks access to Arcee's guns.
- The "Cybertronian Artifacts" hidden throughout the levels bear great resemblance to the Spark extractor from Prime.
- Dreadwing, Starscream, and Airachnid appear together in the game, but not in the tv show.
- Thunderwing is made up of dark energon, very similar to Unicron in the show. The final Thunderwing battle zone is a volcanic area, also very similar to the beginning where Optimus fights Megatron of One Shall Rise, Part 1.