The Story Mode gameplay consists of two Episodes with multiple stages that are unlocked as the previous stages are completed. Within each stage, up to four characters can be playable (One player, 3 AI). Before starting the stage, the player can choose which character to play as, and which characters to set as the AI.
Each stage consists of different rooms, each room must be cleared of enemies before proceeding to the next. Each stage has a specific goal or objective, which must be completed in order to finish the stage.
Weapons dropped by enemies may be picked up if you are not holding a weapon. You may hold up to two weapons at once. Special weapons, such as Sanford's hook cannot be discarded. Sanford's hook, which is a melee weapon, also acts as a ranged weapon when the throw button (E) is pressed. It then returns to Sanford.
Along with a health bar, you also have a TAC-BAR. The TAC-BAR consists of four bars, and recharges over time. When you are hit, the TAC-BAR loses a bar. As long as the bar does not empty, your health with not degrade. A.T.P. engineers and A.T.P. soldats also have TAC-BARs of their own how many bars they have is depending on what difficulty you set it to.
Each time an enemy is killed, the bullet-time meter increases.
After at least one kill, the player may press Shift to enter bullet-time, where all movements are reduced to slow motion. However, certain perks in Arena Combat Mode keeps the player's movement speed intact and having low health will end bullet-time prematurely.
In the Episode 1.5, when you reach half-way all the 5th stage (Vaults), the player will get a halo and the bullet-time switches to Magic Bar. When the player presses Shift, Dr. Christoff will pull out some dark beam for his hands or eyes, which will hit the ground, knocking over all the enemies near him. When the player holds Shift, he will throw the beam in front of him and whoever touches the beam will disintegrate upon impact (unless it is a enemy with many lives, or zombies).
Interactive items, such as lockers or doors, can be opened with the spacebar to reveal extra weaponry, or to prime explosives on objects to destroy them.
Episode 1: Project Nexus
This level serves as the game's tutorial. Hank is the only playable character in this stage, the goal of the stage is to locate Sanford and Deimos and help them escape.
"We're in danger of Nexus Units advancing their equipment loadouts. Hank is required elsewhere, so Sanford and Deimos will have to infiltrate the Armory and put an end to the Nexus weapon stockpile."
"Opposition is getting stiff. The probability of hitting the Headquarters of Project Nexus with any reliability will be nil unless we can disrupt its communications array."
"With Nexus Units reeling from the satelite blackout, we may now launch a stealth strike directly against their most precious and plentiful resource: their manpower. Kill them all!"
[1-E] Recon Hut
"With the Communication Tower down and the Barracks totally obliterated, the Nexus has been forced to adapt. Engineers have been dispatched to convert a nearby Recon Hut into a new Com-Tower. Disable the facility."
An M203 can be found in one of the lockers.
"Intercepted transmissions report the deployment of new G03LM Mk1 units for training at the Nexus Stronghold. Infiltrate the facility, learn what you can, and eliminate this new threat."
Sanford and Deimos are playable characters in this stage, the goal of the stage is to kill all the G03LM enemies within the Stronghold. To kill the G03LMs, you must hit them with melee attacks until their faceplate falls off. Then, you must shoot their head: they are immune to attacks on any other armored part of their body and most melee attacks will not reach their heads.
"It's time to prepare for the final assault on the Nexus Headquarters. A nearby bar is operating as a front for a munitions depot, and hitting this location will benefit us twofold: we'll be well-equipped for the final battle, and Nexus morale will plummet."
Sanford and Deimos are playable characters in this stage, the goal of the stage is to get to the munitions deposit. This is also the stage where you fight the G03LM Mk2. It should be noted that a large majority of the weapons in this stage are bottles. As of the v1.8 update, Krinkels, Luis, Cheshyre, and The-Swain are included in the room with the 'Welcome New Employees' banner. A.T.P Soldats make their debut here.
[1-H] Nexus H.Q.
"Agents Sanford and Deimos will follow Hank into the heart of Project Nexus and eliminate all threats. The Nexus Training Program is still a mystery to us. Discover what you can, and take no prisoners."
Hank, Sanford, and Deimos are playable characters in this stage, the goal of the stage is to uncover Project Nexus. Mag Agent: N is the final boss of this stage. On Floor B-1, where the terminal to release the first set of spikes is, the binary sword can be found in a wall safe.
Episode 1.5: Ground Zero
The sky is some reason red and black but not white, it might be a mistake since Hank killed the sun 15 years in the future.
Dr. Christoff is the only playable character in this episode.
"Fifteen years ago, Project Nexus was the highlight of Nevada's research into resurrective cloning, thanks to the efforts of Dr. Christoff, the program's chief scientist. Reports vary, but something is said to have gone terribly wrong..."
The goal of this stage is to escape the Sci-Post after an apocalyptic zombie outbreak (instigated by Christoff) in the cloning facility.
"In the distance lay the Science Tower, the seat of all Nexus research, and only the eccentric Dr. Hofnarr had high-level access. Christoff's treason would be short-lived if Hofnarr could not be convinced to turn against the organization."
"Once again on his own, Dr. Christoff began his race to the top of the tower. The outbreak would not be contained for long, and the experiments of Project Nexus proved to be more dangerous than their creators."
"Continuing his ascent, Christoff waded through hordes of Nexus abominations. He cringed at what his science had been used to create, eager to reach the end of his climb and make those responsible pay for what they had done."
The goal of this stage is to fight through the chapel in order to reach the the third floor. Sleepwalker patients and Sleepwalker GO3LMS debut in this stage. Phobos, armed with the binary sword, is fought near the end of this stage.
"Nevada itself was on the brink of collapse under the weight of the Project's perverted science. Time was running out, and with no way to know what terrible thing the Nexus would throw at him next, Dr. Christoff prepared for the worst."
Once again, the goal of this stage is to reach the next floor. The halo is obtained in this stage.
"The bulk of the tower now miles beneath his feet, Christoff set his sights upon his prize: the very artifact powering Project Nexus itself. With it in his posession, he would finally strip the program and its insidious masters of all power. God help them!"