The story is set decades after the first Shin Megami Tensei, in the encapsulated city Tokyo Millennium, which is ruled by the religious Messians from a unit called the Center.

The player takes the role of a gladiator who is told that he is the Messiah, and is sent on missions around Tokyo Millennium to eradicate demons and prepare for the Thousand-Year Kingdom.

[1] The gameplay is similar to that of the first Shin Megami Tensei:[2] the game is controlled from a first-person view,[3] and has the player exploring dungeons[4] and navigating outdoor areas, which are presented as 2D maps seen from a top-down perspective.

Opposing both sides, a man called the Hero created a world where both Law and Chaos could co-exist, where people had freedom to choose and believe what they wished.

Hawk wins the gladiator tournament in Valhalla, gaining citizenship in the Center, and is asked by Hiroko to help her find a boy who has gone missing.

The Center sends Aleph and Beth on missions across Tokyo Millennium to eradicate demons and prepare the world for the Thousand-Year Kingdom.

Aleph and Hiroko learn that the elders are actually the archangels Michael, Raphael, Uriel and Gabriel; Aleph and Hiroko fight and kill the first three archangels, after which Gabriel reveals that YHVH, the creator god, had ordered the archangels to watch over the creation of Tokyo Millennium and wait for the Messiah, but that Michael, Raphael and Uriel, unable to wait any longer, created Aleph as an artificial, false Messiah, leading YHVH to abandon them; he was the boy Hiroko was searching for, aged unnaturally fast to take on the role of Messiah.

Leaving Lucifer's castle, Aleph and Hiroko meet Gabriel, who takes them to the garden of Eden, located on top of the Center, where they meet Zayin – revealed to be Satan (after Zayin merges with the demon Set) – who wants to ally with Aleph and Hiroko and fight Lucifer, destroy Tokyo Millennium, and create the Thousand-Year Kingdom.

If the player joins Gabriel and Zayin, the Thousand-Year Kingdom is created through Eden — revealed to be a vast spaceship carrying the chosen ones — and the destruction of all life on Earth.

[7] It was directed by Kouji Okada, produced by Hideyuki Yokoyama,[8] and written by Ryutaro Ito,[9] with music composed by Tsukasa Masuko.

[11] During the game's pre-production, the development staff visited Hariti's temple in Zōshigaya and Taira no Masakado's grave to cleanse themselves.

The two had different ideas about the timeline of the series, but eventually decided to set the game "several decades" after Shin Megami Tensei.

[9] According to Kaneko, the reason for choosing the Judeo-Christian-Islamic god, YHVH, as the game's antagonist, was that he saw YHVH as the base for all other gods around the world: Having observed common motives throughout different mythologies, such as the flood and the creation of the world, he reasoned that they all originated in one single mythology, which had been changed as people took it with them, leading to modern-day myths.

[1] Aleph was created to embody the Shin Megami Tensei II world, which is reflected in his character design: he has a portable computer and a visor that he controls demons with, and carries swords, guns and armor for use in battle.

[12] Beth and Daleth were designed to look similar to the first Shin Megami Tensei's Heroine and Hero, using the colors blue and green, respectively.

[2] Kalata and Snelgrove did not think the game's story started "with the same pizzazz" as Shin Megami Tensei; they thought that "the amnesiac savior" is a "lame cliche", and that the idea that Western religion is evil has been worn out.

[14] A popular urban legend in Japan is that there is a 1/65536 chance of the game's intro freezing and displaying the red text saying "Sugu ni Kese" (Japanese: すぐにけせ, lit.

[22] The special gifts for pre-order players of Shin Megami Tensei IV include a printed eraser with the message "Sugu ni Kese".

[23] In June 2023, a Chinese leaker referenced the urban legend to tease the announcement of Shin Megami Tensei V: Vengeance.