It is a prequel to Resident Evil (1996), covering the ordeals experienced in the Arklay Mountains by special police force unit, the S.T.A.R.S.

The story takes place in July 1998 and follows officer Rebecca Chambers as well as convict Billy Coen as they explore an abandoned training facility for employees of the pharmaceutical company Umbrella.

The partner system was created to take advantage of the short load times possible with the capabilities of the Nintendo 64 Game Pak.

Inspired by Sweet Home (1989), the team removed the item storage boxes present in earlier games and introduced a new item-dropping feature.

The game was ported to the Wii in 2008, and a high-definition remaster was released in January 2016; the rereleases received mixed reviews due to lack of improvements.

In contrast, Billy can move heavy objects, use a lighter, and has higher defense, but cannot mix herbs (a staple ability in Resident Evil games).

As she explores the train, she teams up with Billy Coen—a former Marine Force Reconnaissance officer, who was to be executed for killing 23 people until the military police van transporting him crashed in the region.

Unbeknownst to the pair, two soldiers from Umbrella, on the orders of Albert Wesker and William Birkin, attempt to take control of the train and destroy it, but are killed by leeches before they can complete their mission.

He combined it with leech DNA to develop the T-virus that causes rapid mutations in living organisms and thus transforms humans and animals into zombies and monsters.

As the pair continue to explore the facility, Wesker decides to leave Umbrella and join its rival company, and makes plans for further research on the T-virus.

On her own, she encounters Captain Enrico Marini, who tells her that the rest of the Bravo team will meet up at an old mansion they found, but allows her to stay behind to find Billy.

After his corpse was dumped, the Queen Leech entered his body and reanimated it, gaining his memories and the ability to shapeshift, thus believing itself to be the resurrected Marcus and orchestrated the T-virus outbreak in the facility and on the train as a means of revenge against Umbrella.

After temporarily defeating it, Billy and Rebecca attempt to escape to the surface via a lift, just as William Birkin trips the facility's self-destruct mechanism.

Thanking her for his freedom, Billy departs as Rebecca heads towards the mansion to seek out the whereabouts of her fellow Bravo Team members, setting the stage for the events of Resident Evil.

For these reasons, the team approached Resident Evil Zero with different ideas for gameplay and visual design that would function better with less storage space.

[8] After the script had been completed in early 1999, the production of a Resident Evil game for Nintendo 64 was revealed to the public by Yoshiki Okamoto, the president of Capcom's screenplay company Flagship.

[9] Resident Evil Zero was designed to be more difficult than its predecessors, removing the item boxes to make the game more like Sweet Home (1989).

[10] The real-time "partner zapping" system was designed to take advantage of the console's unique features and strengths, namely the lack of load times, which are necessary for optical disc based gameplay as with the PlayStation.

[8] Resident Evil Zero was officially announced at 20 percent completion in January 2000, after which it was presented with a playable demo at Tokyo Game Show.

[16] The game's final version was developed primarily by Capcom Production Studio 3 with additional support provided by Tose.

[22] The GameCube's use of optical discs reintroduced load times, so the programmers had to use sophisticated programming to make the "partner zapping" system work.

[29] The success of the high-definition remaster of Resident Evil inspired producer Tsukasa Takenaka to provide the same treatment to that game's prequel.

This meant that some assets had to be redone, as items that were intentionally blurry or illegible in the original were now much more clear and did not make sense in context, such as posters or signs in the environment.

[3][38][42] Scott Steinberg of GameSpy noted how the animated backgrounds, such as flickering lights and dripping water, brought the environments to life.

[43] Giancarlo Varanini of GameSpot shared these sentiments, and complimented Capcom on how they were able to blend the game's models with pre-rendered backgrounds to create highly detailed visuals.

[42] The sound design was also complimented, with Matt Casamassina of IGN noting that "Capcom uses silence at times, too, to scare, which is brilliant.

"[42] Louis Bedigian of GameZone praised the sound effect work, such as thunder, gunshots, and footsteps for building a scary environment.

[42] Bedigian of GameZone praised the companion system for adding a new dimension to the Resident Evil series and it left him excited for future games.

[49][50] For the high-definition remaster, critics were impressed by the improved visuals but ultimately felt the game inherited the problems of the original.

[36][51] Peter Brown of GameSpot highlighted Wesker Mode as a fun addition and noted the game still "bears the hallmarks that made the original Resident Evil enjoyable.