When a strange symbol appears on Voyager's computer screens, Janeway begins giving orders without explanation. She is carrying out a highly classified mission called the Omega Directive, and Seven of Nine is the only other person who knows what it means. Voyager's sensors have detected the Omega molecule, which is a highly unstable phenomenon. Janeway's orders as a Starfleet Captain are to destroy it, but Seven believes its power should be harnessed. The Borg believe it represents perfection. She agrees to help Janeway carry out the Directive so she can study the molecule more closely.

When Chakotay convinces the Captain she needs the resources of her crew, Janeway briefs the senior staff on the Directive. The Omega molecule is the most powerful substance known to exist and could create a subspace rupture that would make warp travel impossible. The crew sets a course for the molecules, knowing that this mission must succeed, or they will never make it out of the Delta Quadrant.

Seven begins working on a harmonic resonance chamber, which should stabilize the Omega molecule, while Janeway leads a rescue mission. She has found a planet where researchers were working to create a molecule when an explosion left them exposed to radiation. Before being beamed to sickbay, the senior researcher tells Janeway one of the Omega molecules survived in the primary test chamber. When Seven questions him later, he pleads with her not to destroy Omega, saying that the discovery of the phenomenon is the lifeblood of his people.

Once she breaks into the test chamber, Janeway finds enough Omega to wipe out half of the Delta Quadrant. To destroy it with Seven's harmonic resonance technology, the molecules must be transported to Voyager. Yearning to understand Omega's perfection, Seven no longer believes it should be destroyed. After the molecules are safely beamed into containment, the crew takes off with several alien ships in pursuit.

In an open area of space, Janeway prepares to jettison the chamber containing the molecules and then destroy it with a torpedo. Seven manages to neutralize almost half of the molecules, and just before the chamber launches, she witnesses them stabilize spontaneously. Once the torpedo is fired, Voyager escapes at maximum warp, leaving behind no trace of Omega. Janeway has successfully carried out her Directive, and Seven has had her first spiritual experience.