Star Trek: Armada II employs many of the same features of its predecessor, though with a few improvements. The game ends with the two sides parting ways, the Klingons asserting control over the Cardassians and order, somewhat, returning to the galaxy. The Federation and the Borg Collective create an alliance and venture into Species 8472's fluidic space to destroy their staging grounds by destroying the Rift Maker, thus ending the threat to the Alpha Quadrant by closing all the rifts. She then realizes that only by working with the Federation they can defeat Species 8472.

She attempts to mass an armada to suppress this threat by assimilating native species planets, ships and technologies, but its growth is stunted by the constant attacks from the Federation. The Borg Queen, stranded in the Alpha Quadrant by the same twist of fate that trapped Picard on her side of the galaxy, discovers that Species 8472 has found a way into the Alpha Quadrant. In the final battle, Martok tracks down and kills Gul Kentar, taking out the Quantum Singularity Project along the way. The Klingons stop the Cardassian rebellion and occupy their homeworld, Cardassia Prime. Martok leads an attempt to thwart Kentar's grab for power and destroy the project. Kentar is developing the 'Quantum Singularity' that allows the Cardassians to summon Species 8472 ships at will.

Klingon Chancellor Martok discovers that Gul Kentar, leader of the Cardassian uprising, is in league with the Romulans.

The Cardassians proceed to destroy the Federation's reserve fleet. Meanwhile, the Cardassians use the sudden absence of Federation forces to begin their own offensive. Though successful, some of the Federation forces, Picard included, are left stranded when the Transwarp Portal collapses due to a destabilization of the inter-spatial transwarp manifolds. Starfleet Command then orders Picard to seize control of it and launch a counteroffensive into the heart of Borg space in the Delta Quadrant, into the Borg staging grounds. Intrigued, Picard discovers a new type of transwarp gate called a Transwarp Portal, capable of sending fleets of starships from one quadrant to another almost instantly, thus giving reason as to how the Borg managed to get so deep into the Alpha Quadrant undetected. After routing the attempted foothold, Captain Picard discovers a new type of nebula - a tachyon nebula. They have created a new ship capable of assimilating entire worlds in just a few seconds. PlotSet just six months after the events of Star Trek: Armada, the Borg once again threaten the Alpha Quadrant.

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