In Greek mythology, Orthrus was a two-headed dog and one of the many monsters sired by Typhon and Echidna. Among his siblings were Cerberus, Sphinx and Chimera to name but a few. Orthrus was the dog of the TitanGeryon, and along with Eurytion, was the guardian of Geryon's herd of red cattle. Geryon, Eurytion and Orthrus were all slain when Hercules ('Heracles' in Greek mythology) was completing the tenth of his twelve labors.
Orthrus appears as a servant of Pazuzu, and worked alongside the partner before she broke away from Pazuzu's control. After reaching the ruins of Tokyo, Pazuzu instructs the hero and his friend to meet up with Orthrus at the Princess Hotel and assist him in taking out the partner. During their confrontation with her at Tokyo Tower, the hero ends up siding with her and the friend and Orthrus part ways with him. Orthrus continues to fight alongside the friend after his transformation into the Dark Hero, but is killed in battle with the hero's party.
Shin Megami Tensei
"Origin: Greece. A two-headed guard dog as large as a bullock. This dog was kept by the monster Geryon in Erytheia, the island at the world's end. It was killed by Hercules, who came to steal the red cattle that live there."
—Shin Megami Tensei A-Mode DDS Dictionary
Shin Megami Tensei IMAGINE
"A gigantic, two-headed dog, the child of the storm giant Typhon and the half-snake beast Echidna. His body is as big as an ox, and he has the fearlessness and ferocity of a lion. Orthrus guarded the underworld alongside Cerberus, but was also said to guard the herds of the monster Geryon, who lived on the island of Erytheia at the edge of the world. However, he was killed by a blow from the club of Heracles, who came to the island as part of his Twelve Labors. He also fathered the Sphinx, the Nemean Lion, and other monsters with his mother Echidna."
—Shin Megami Tensei IMAGINE Compendium
Orthrus appears on Suginami field and within the gold level instance of Suginami Tunnels and the Nakano Stone Site. He can be contracted during the daytime in Ikebukuro outside the gates of Zoushigiya Cemetery. He appears regularly as a field boss in Suginami and alongside Cerberus and Garm as the final bosses of the Suginami Tunnels Unknown boss rush. He is also one of the mountable demons within the game.
Shin Megami Tensei: Strange Journey
"The two-headed dog who protected the titan Geryon's red cattle in Greek lore. Despite his skill as a guard, Hercules killed him in one blow while performing his Twelve Labors."
—Shin Megami Tensei: Strange Journey Compendium
Shin Megami Tensei IV
Orthrus appears as a boss on the second stratum of Naraku. Flynn is required to defeat it as part of Navarre's challenge to him and Walter.
Shin Megami Tensei IV Apocalypse
"The two-headed dog who protected the Titan Geryon's red cattle in Greek lore. Despite his skill as a guard, Hercules killed him in one blow while performing his Twelve Labors."
—Shin Megami Tensei IV Apocalypse compendium
Orthrus can be found in Ikebukuro or evolve from Chimera once it reaches level 50. Orthrus can also teach Nanashi the Fire Breath, Nihil Claw, Eat Whole and Madness Nails skills through its Demon Whisper. It benefits from learning Physical and Fire skills. Orthrus will evolve into Cerberus at level 64, provided that Nanashi can control the result.
Devil Summoner: Soul Hackers
"The two-headed dog who, along with his master Eurytion, protected the Titan Geryon's red cattle in Greek lore. When Hercules went to claim Geryon's cattle for his tenth labor, he slew Orthrus with one swing of his club."
—Devil Summoner: Soul Hackers 3DS Compendium
Devil Summoner: Raidou Kuzunoha vs. The Soulless Army
"The two-headed dog who protected the titan Geryon's red cattle in Greek mythology. Despite his prowess as a guard, Hercules killed him in one blow while performing his Twelve Labors."
Orthrus appears both as a Persona of the Hanged Man Arcana and as a weapon for Aigis.
Persona 5
"The two-headed pet dog belonging to the giant, Geryon, in Greek myth. He guarded a herd of red oxen, but was killed by Hercules during one of his twelve labors."
—Persona 5 background
Orthrus may be encountered as a Shadow in the initial areas of Kaneshiro's Palace, with the title of Twin-Headed Guardian.
DemiKids Light & Dark
"Fire-breathing demon and brother of Nex. Can burn foes to a crisp."
Known as Orthros, he has the power FireWall. Orthros can perform the combo Fire Flare with Demipyre and Evil Blaze with Nex or Pyro Cat.
Devil Survivor 2
"The two-headed dog who appears in Greek lore as the younger brother of Cerberus. He protected the titan Geryon's red cattle, but despite his skill as a guard, Hercules killed him in one blow while performing his Twelve Labors."