G-Nome casts the player into the shoes of Sergeant Joshua Gant, a retired Union Intelligence Agency operative who has been out of action since a disastrous mission took place ten years prior in 2215 A.D., in which his closest friend, Ron Pearl, was lost and presumed dead, due to the fiendish negligence of the unscrupulous Major Jack Sheridan. Now, in 2225 A.D. a mineral-rich Phygos star system has been discovered at a critical location within the Milky Way, causing the tactical mobilization of the Darken Republic, Bendian Mercenaries, the Union and the Scorp Empire. The U.I.A. has recently uncovered a biological weapons program developed by the Scorp Science Corp., which involves modifications of the human genome, which has bread an incredibly dangerous monster known as the "G-Nome". The most controversial matter is that there are indicators that human P.O.W.s have been used as test subjects for the experiments. Therefore, Gant is reinstated as an operative, with a ground-based mission of killing the G-Nome and destroying the facility where it is kept.
The mission commences in the desert of the Darken Republic, which Gant infiltrates after a brief skirmish with a small Bendian raiding party. He is informed that his former squad member and friend, Stephen Kylie, has left coded messages across the Darken territory and that he is awaiting him near Chambers Pass, located at the Darken-Merc frontier. After having his stolen Darken Sentry HAWC confiscated by the border control agent Commander Alm'sh Kor, Gant slips in with her convoy en route to the regional headquarters, where he learns that he must acquire Kylie's radio signal from the regional LATLON Communitcations Array. Gant's first major combat experience occurs at the array, where he destroys the array and its defenders. Upon decoding the final message, Gant discovers that Kylie's cver is blown. With their communications disabled, Gant fights through the Chambers Pass border guard and meets up with Kylie.
Finally in Merc territory, Gant and Kylie attempt to receive a dropship rendezvous package that includes two Union HAWCs, but due to a leak, the dropship crew is lost and the Mercs steal the vehicles. After destroying the vehicles intended for them and receiving replacements, the duo determine that their next squad recruit, genetic scientist Doctor Victoria Thane, is in danger. Gant and Kylie move quickly to destroy the Merc's LATLON Communications Array and after an intense battle with a large Merc raiding party, they rendezous with Thane. Thane is informed by U.I.A. Director General Allance Wilkins of the G-Nome situation. She concludes that the method to destroy the creature would be to obtain a neural inhibitor from the Merc compound that houses a citadel atop Mesa Caracon. The team resupplies with Merc vehicles and make their way to the base of the mesa and infiltrate the facility. The Mercs become aware of this, however, and dispatch a wave of attack fighters to eliminate the Union combatants. After a short battle, Thane obtains the needed materials and the group escapes into Scorp territory.
Near the Scorp frontier, the Union agents find that the border crossing is heavily defended and the only realistic way to proceed would be to join a recon convoy, using stolen indentifier codes. This plan produces terrible results, however, as the convoy is confronted by an off-course Union patrol, which Gant is forced to help destroy. Inland, General Wilkins informs the team that their final squad member is none other than Sheridan, who is the Union's single-greatest expert on Scorp culture and technology. Sheridan directs an assault on the Scorp's LATLON array at Ur-Kinsk, which allows for the team to assault the weapons depot of Ur-Ulit, in order to obtain Scorp vehicles that have imaging technology to uncover mine fields. Once the vehicles are obtained, the team assaults Ur-Alr, which has a headquarters that contains the coordinates of the G-Nome laboratory itself. The team defeats the Scorp Elite Peacekeepers and arrive at the facility and after Gant destroys it, Sheridan shows his true colors by attempting to kill Gant and capturing the G-Nome. Kylie is captured by the Scorp and held at the regional headquarters, where Gant and Thane attempt to rescue him, but they themselves are captured by the Scorp Directorate Prees Tak. Unexpectedly, Tak agrees to team up with the U.I.A. and fight Sheridan's forces that attempt to overwhelm Ur-Kinsk. Despite eliminating the sizable army, they discover that it was simply a diversion for Sheridan's main column to escape into the volcanic Shalton frontier, where Sheridan's alleged recombination lab is hidden.
The Scorp see Gant and his team off. After encountering multiple Darken and Merc firefights, the team allow for reinforcements, including General Wilkins, to arrive and assault Sheridan's heavily-defended lair. Satellite imaging, however, indicates that Sheridan is making an attempt to transport D.N.A. samples off-planet and their time is short. In command of the powerful Union Heavy Assault HAWC, Gant fights through Sheridan's forces alongside Kylie and destroys the lab. As the remaining renegades are taken care of, however, Sheridan personally kills Kylie and attempts to flee with the G-Nome. Gant gives chase with a vengeance and after one-on-one combat, kills Sheridan. Picking up the neural inhibitor device from Sheridan's corpse, Gant approaches the battered cargo bay that holds the G-Nome and makes his stand. The creature attacks Gant, but is quickly neutralized by two shots from Gant's weapon. Gant notices a bar code on the G-Nome's paw and looks closer to see that it reads "R. PEARL". Shocked, Gant contacts Wilkins and hesitantly informs his superior that not only was Sheridan dead, but the G-Nome was killed. As the creature awakes, Gant yells for Pearl to escape. The last image seen is of the G-Nome walking into the sunset.
Following the G-Nome's escape, Union agents swarm and inspect Sheridan's lab. Wilkins, however, is transfixed upon a pitri dish amongst the remains, which reads "G-NOME: PEARL". As the Union forces begin to move out, Wilkins snatches up the dish and disappears. Soon after, the Scorp Imperial Tribune officially declares war of the Union. Public knowledge of the mission is minimal; the only indication of its existence is the unexpected resignation of Wilkins. Both the Union and the Scorp deny the mission, to the mystery of all.