The entirety of G-Nome's gameplay is based around close-surface combat, by the means of direct foot movement or the occupancy of vehicles. The majority of the vehicles are bipedal assault machines called "HAWCs", (Heavy Armored Weapons Chassis), that usually carry between two and four weapon mounts, which vary between laser pulse weapons, machine guns and missiles. Aside from the HAWCs, each of the races in the game maintain hovercrafts and armored support vehicles, for strategic insurance and variability.

The game takes place in the year 2225, A.D., on the remote world of Ruhelen in the Omicron Reticuli star system. This planet has been a contested territory between the Darken, Union, Mercs and the Scorp, which are the Union's greatest threat. The discovery of the mineral-rich Phygos star system nearby has upset the tenuous strategic balance of the four races, leading to speculation of an inevitable war. The player assumes the role of Sergeant Joshua Gant, a retired Union Intelligence Acency, (UIA), operative, who for ten years prior, has been experiencing horrifying nightmares from a mission that resulted in the loss of his best friend and comrade, Ron Pearl. Following one of Gant's nightmares, the sergeant is contacted by UIA director General Allance Wilkins, who reinstates Gant immediately for a mission of the utmost importance. According to Wilkins, the Scorp have been conducting top-secret biological warfare experiments upon human prisoners of war, in order to create a mutated super-soldier dubbed the "G-Nome". Gant is commanded to euthanize the G-Nome and destroy the Scorp facility that has been housing the experiments. For assistance, Gant is assigned a team that includes his old friend and munitions expert, Sergeant Stephen Kylie, Union's most accomplished geneticist, Doctor Victoria Thane and an undisclosed final member of the team operating within the Scorp territory.

Gant begins his mission by traversing the Darken Republic on foot and strategically taking out any opposition that would hinder his objective of rendezvousing with Kylie. United once again, the duo embark across the Merc territory to meet Thane, who has been on a separate assignment. Upon Wilkins' disposition, Thane identifies some specialized Merc technology stored away at a facilitated structure called the Citadel upon a mesa called Caracon as the means of neutralizing the G-Nome. After acquiring the technology, the team heads for the Scorp territory.

Gant and his team bypass the heavily-defended Scorp border, where he is introduced to the final member of his team: Major Jack Sheridan, a Scorp specialist and the man responsible for the loss of Pearl ten years prior. After several precarious skirmishes with the intent of acquiring Scorp vehicles for bypassing mine fields and learning of the G-Nome facility's location, Sheridan leads the team directly to the laboratory. The mission is compromised, however, when Sheridan attempts to kill Gant, captures the G-Nome and allows for Kylie to be captured by Scorp reinforcements. Soon after, however, the Scorp ally with Gant, with recognizing Sheridan and the G-Nome as a greater threat. The Scorp and UIA realize that Sheridan has a genetic recombination laboratory located within the volcanic Shalten Frontier, where not only is he backed by a sizable army, but he intends to clone the G-Nome.[6]