One day, while on a space walking experiment, an accident occurs when Jonathan suddenly loses control of his suit and is sent drifting away in space from his colleagues. 25 years later, Jonathan is found alive and well thanks to the cold sleep module in his suit. In addition, it also retained his youth. The year is now 2040, and Jonathan is working as a private investigator in Old Los Angeles when he is visited by his ex-wife Lorraine, who is now married to Kenzo Hojo. She attempts to hire him to help find Hojo, who had suddenly disappeared. The only clues to his disappearance are a torn leaf, a set of capsules, and the word "Plato". Jonathan is reluctant to accept the case at first, but as Lorraine is leaving, she is attacked and murdered by a mysterious masked motorcyclist using a car bomb. Jonathan chases the motorcyclist but is unable to apprehend him.
Following Lorraine's death, Jonathan travels to Beyond Coast where he meets with a man with grey skin and purple hair named Tony Redwood. Eventually, the plane arrives at Beyond Coast.
With the information, Jonathan and Ed travel to Tokugawa Pharmacy R&D. They meet with the security guard, who lets them into the DDS room, and notice a T-GEAR 99 computer. They also notice a calendar mention something about Wednesday the 15th and BCCH. After a while, the two drive to the Hojo residence, where they meet with Karen Hojo. Karen is upset at Jonathan over her mother's death, but eventually calms down before allowing the two to enter her house. While talking with Karen, she mentions HLA and Beyond Coast Central Hospital. They then enter Kenzo's study, where they find his ID card and a small Kamon list.
After talking with Karen, Jonathan and Ed drive to BCCH, where they meet Chris Goldwin. It appears that she does know about Kenzo and HLA, but during the conversation her pet mosquito suddenly breaks loose, and Jonathan eventually catches it. After talking with Chris, Jonathan and Ed then meet with Ishida in the hospital's supply room. It seems he too knows about Kenzo. They also notice a computer similar to the one in the pharmacy in the supply room.
The two detectives make their way to the Tokugawa tower, where they arrive at the 40th floor. They notice a party going on, and they also meet with Salvatore Toscanni, Joseph Sadoki Tokugawa, and Chris. When Jonathan talks to Tokugawa, he accuses him of being responsible for Lorraine's murder and Hojo's disappearance and an argument breaks out, only for Ed to restrain Jonathan and flee.
Upon arriving at the museum, Jonathan and Ed meet with the informant, who reveals that NARC is K-9, and that Kenzo had a CD-ROM containing vital information. Eventually, the informant leaves, and Jonathan and Ed return to the Hojo residence to find the CD-ROM. However, when returning to the pharmacy, they notice the computer is gone, so they must go to the hospital and play the CD-ROM on Chris's computer from there. After the presentation, the two return to the police station and talk with Victor. They also notice Tony holding a capsule, but oddly enough it's not NARC as the Tokugawa logo is incomplete. After talking with Dave and Meryl, Ed mentions something about the AMM, so they travel back to the museum.
Back at the museum, Jonathan and Ed notice something unusual going on. The Policenauts statues have been vandalized, with Jonathan and Ed's heads missing. They also notice that the informant has also been decapitated, and it turns out that the informant was Ishida. Robotic mosquitoes then attack the pair, and Jonathan is forced to fight them off. Jonathan also has to defeat an attacker at the Apollo Exhibit before clearing out the mosquitoes using a fire extinguisher.
Back outside, as Jonathan and Ed try to recap what had happened so far, they suddenly notice a mysterious figure underneath their car. It turns out to be the same masked bomber who had killed Lorraine. As the masked man escapes on his bike, Jonathan and Ed pursue the man in their car down the highway. Jonathan manages to spill the man off his bike, and pursue him to a train station. The masked man boards a train and takes Chris hostage in the process. He eventually escapes and Dave and Meryl corner the man. Dave is shot during the fight and dies in Meryl's arms, but not before revealing the man was Redwood in his last moments.
Jonathan and Ed track Redwood to a nearby bag shop, but he had already escaped. In the process, he also left a bomb inside one of the bags, and after safely removing all the fake bags in the shop, proceed to work on disarming the bomb. After defusing the bomb, the two head back outside and notice a few EMPS take off with one of them bleeding.
At the pharmacy, Jonathan and Ed check out a room they haven't entered yet. There, they notice a factory where the poppy flowers are being used to manufacture the drugs. With this information, they report back to Gates and the police organizes a raid on the pharmacy. However, when they arrive, all the evidence of NARC being manufactured has been erased. They also discover Kenzo's corpse at the plant, and Jonathan is then arrested for murder.
After suffering from a nightmare, Jonathan finds himself back at the Hojo residence. It turns out that Jonathan had been broken out following his arrest, and is now on the run from the authorities. He turns on the news and finds out about the car accident, as well as Gates at a press conference about Jonathan, the Policenauts, and NARC. Ed then contacts Jonathan, and tells him to meet with him at the hospital.
At the hospital, Jonathan is overlooking Ed and Karen. It turns out that Karen's illness is kicking in, and she needs a bone marrow transplant to save her life. The doctor takes some of Jonathan's blood, and Meryl reveals to Jonathan that the reason why he was unable to shoot Redwood is because long ago, the man Ed had killed was not only Marc's father, but Redwood's brother, Ridley. Jonathan then deduces that Chris is in on the conspiracy, and catches her before she could kill Ed. As Chris tries to spill the beans, she is suddenly gunned down by Redwood in his EMPS, and Redwood challenges Jonathan to come to the Tokugawa building for a final showdown. Jonathan eagerly accepts.
Following Redwood's death, Jonathan arrived at the 40th floor, where Jonathan is confronted by Gates, piloting a larger and powerful EMPS suit. Gates goads Jonathan into shooting him, and when he does, the recoil ends up propelling him backwards due to the lack of gravity. Gates then shoots Jonathan several times before revealing the reasons why he and Tokugawa have smuggled the organs and talks to Jonathan about the harshness of outer space. Eventually, it's revealed that Jonathan had recorded Gates's speech the entire time, therefore exposing their plans. Enraged, Gates prepares to kill Jonathan only to be shot in the head by Ed. Jonathan and Ed then make their way to the lobby, but are confronted by Tokugawa, who reveals he had shut off the broadcast. He then orders the AP to kill the two, but Meryl and the other police officers arrive and arrest Tokugawa. As a result of the blood test from earlier, it turns out that Jonathan's bone marrow is what's needed to save Karen.
In a post-credits scene, Jonathan narrates that no matter how far humanity travels into space, they will never forget about Earth, their birthplace, and will always watch over her.
