At the same time, Meryl Silverburgh with three other members of Fox-hound have been sent to investigate the activities of Liquid Ocelot's private military company (PMC). Meryl's team includes her second-in-command Ed, electronics expert Johnny (aka Akiba) and Jonathan. Meryl, Ed, and Jonathan have the ability to share each other's senses via their internal Sons of the Patriots nanomachine network.

In addition, Naomi Hunter, the chief of Fox-hound's medical staff and part of the support crew, has been kidnapped by Liquid Ocelot and is begging Snake to rescue her.

Snake, along with his close friend, master engineer Octacon, vow to defeat Liquid before he can achieve his goals.

1. Old Snake (aka Solid Snake): Veteran ex-Fox-Hound member and deep cover CIA agent
2. Otacon: Scientist with Engineering Research Facility
3. Raiden: Adopted son of Solidus Snake; former child soldier in the "Devil's Army" during the Liberian Civil War
4. Naomi Hunter: Fox-Hound's medical department director

1. Sunny: computer programmer and daughter of Olga Gurlukovich from Metal Gear Solid 2
2. Drebin 893: Weapons launderer who disables PMC ID-tagged weapons
3. Roy Campbell: Original executive officer and the second commanding officer of the Fox-Hound unit of special operatives
4. Mei Ling: Fox-hound communicative data processing specialist
5. Rosemary: Psychological counselor and Raiden's former girlfriend from Metal Gear Solid 2
6. Big Mama: Leader of the resistance group Paradise Lost. Voiced by Lee Meriwether

1. Meryl Silverburgh: Daughter of Roy Campbell, fourth and current Fox-Hound commanding officer
2. Johnny (Akiba): Former Genome Soldier and electronics expert. Only member of the team that was not injected with nanomachines. Marries Meryl at the end of the game
3. Jonathan: Korean-American heavy weapons specialist with a mohawk in the shape of an exclamation mark
4. Ed: African-American sniper and Meryl's second-in-command, also a priest/chaplin

1. Liquid Ocelot: Formerly known as Revolver Ocelot, Liquid was a Patriot agent who lost his right arm in Metal Gear Solid and received a transplant from Liquid Snake. With Liquid's personality consuming his mind, he forms the private military company Outer Heaven to destroy The Patriots
2. Vamp: Surviving member of Dead Cell from the Big Shell incident with vampire-like attributes, including taste for blood, the ability to stand on water and vertical walls, superhuman speed and agility, and the ability to survive potentially mortal wounds

1. Screaming Mantis
2. Crying Wolf
3. Laughing Octopus
4. Raging Raven
5. Psycho Mantis

1. Zero: Big Boss's commanding officer and close friend in Snake Eater
2. Big Boss: Former Fox-Hound commander and founder of independent militarized nation, Outer Heaven