She at last reveals to her granddaughter Lucretia what happened on that fateful night in New Way City - as Scarface approached her in the church and removed its bio-helmet, she shot the Yautja in the eye, splashing both herself and her newborn son Hunter with the creature's blood. MOTHER is revealed to be Isabella Borgia, somehow still alive after 100 years, held inside a preserving tank and linked into the city's computer network. Inside, Scarface duels and finally kills the third Bad Blood, before entering the chamber housing MOTHER, the supercomputer that controls Neonopolis. Scarface then follows Lucretia to the Borgia Industries headquarters, where he finds himself within a holographic recreation of 1930s New Way City, including a perfect replica of the church where he confronted Isabella 100 years before. Lucretia Borgia, Bruno's granddaughter and CEO of Borgia Industries, dispatches three cybernetically-enhanced Bad Blood Yautja to stop Scarface he defeats two of them, but the third escapes. Scarface reawakens inside a high-tech Borgia Industries facility, but quickly escapes his bonds, reclaims his weaponry, frees several other captured Yautja and flees the complex. After the Predator has made the kill, he enters a nearby church and approaches Bruno's wife Isabella, who has just given birth to her infant son Hunter, and shows them Bruno's severed head. He stalks mob boss Bruno Borgia to a museum, killing several of his mafia lieutenants along the way, before defeating the self proclaimed 'God of gangsters' in hand-to-hand combat. While he is unconscious, Scarface recalls events on the night he was disgraced in New Way City 100 years before. Scarface raids an underground Borgia depot, destroying it, but is overwhelmed by cyborg troops as he tries to flee and is captured. Upon landing in Neonopolis, the Predator quickly begins massacring the city's gangs, soon learning that the equipment they are using has been supplied by Borgia Industries. Scarface's clan offers him forgiveness if he returns to Earth, reclaims the stolen technology and slays those who would dare use it. His clan returns to him and offers him a chance for redemption - the criminal gangs in the rebuilt New Way City, now known as Neonopolis, are using highly advanced weaponry reverse-engineered from the equipment that Scarface left behind to capture other Yautja and wage mob warfare amongst themselves.

One hundred years later the Yautja, known as Scarface, stands atop a pile of the dead extraterrestrial creatures. As the lone Yautja watches his clan fly away, hostile insect-like creatures emerge all around him and close in. Shamed by defeat and having exposed his race to the humans, the Yautja is exiled by his clan to a remote, desolate planet. As a last resort, he sets off his ship's self-destruct sequence, leveling much of the city but failing to kill himself. As the Yautja crosses a roof, the building collapses beneath him and he becomes trapped in the burning ruins. The game opens in 1930 in New Way City, with a badly wounded Yautja attempting to return to his ship in the middle of a large riot.

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