- Diseased - are humans who are infected with a bacterial or viral infection that causes fatal mutations in humans. Diseased are still able to use firearms, as well as not attack each other.
- Mutates - are those victims in the advanced stage of the infection. Their arms have mutated into tentacles or claws, allowing them to attack at longer range. They attack anything moving including the Maraisreq, the Diseased and each other.
- Soldiers - The G.G.G. uses troops of the Wehrmacht in its operations. They wear green field uniforms and bandoliers and possess basic combat training. They use a variety of weapons, ranging from pistols to heavy machineguns, yet are unable to block Rayne's attacks.
- Waffen-SS troopers - members of the elite Waffen-SS, these troopers wear panzer-like leather jackets and use the same weapons as regular soldiers. However, they are faster, stronger and can block Rayne's melee attacks as well as use combat knives.
- Waffen-SS low-ranking officers (unteroffiziers) - these NCO enemies differ from the regular SS troopers only in that they wear a grey coat. Otherwise, they are almost identical to regular Waffen-SS troopers.
- Jürgen Wulf - he is Nazi officer who founded the Gegengeist Gruppe a group that aimed to sustain Hitler in power through the use of occult artifacts, including obtaining and reassembling the remains of Beliar.
- Báthory Mengele - also known as the "Butcheress", was a Nazi scientist working for the Gegengeist Gruppe. She is sadistic and deranged, the Butcheress is a dangerous individual who enjoys experimenting on innocents. When Rayne watches from afar, she sees the Butcheress kicking victims into the pit of Daemites while laughing maniacally
- P. Eckstein - is a Nazi Officer and a Major of the Gegengeist Gruppe. He worked closely with the Butcheress and experimented with the toxic gas, using the natives as test-subjects.
- Kommando - is a mysterious Nazi officer of Gegengeist Gruppe. He fights with an assault rifle and uses flashbangs to escape from Rayne. Kommando has a very strong tactical background and is highly trained.
- Von Blut - is a thule High Priest. Thoroughly deluded, he believes that Aryans were descended from the people of Atlantis and that Beliar was that nation's great leader, who was torn apart by the destruction of Alantis.
- D. Mauler - was a human cybernetic enhanced by the Nazis. A brute with his physical size and strength greatly enhanced by the Nazis and covered with cybernetic augmentations, thus making twice as tall as a normal human.
- Elite Soldiers - members of the special forces formed within the G.G.G., under the lead of Kommando, are outfitted with red full body armor for protection against bullets, a face covering gas mask and a steel helmet. They use submachineguns, FG-42s and StG44s and can block Rayne's attacks with ease.
- Hazmat Troopers - To handle potentially hazardous materials, the G.G.G. outfitted several of their members with haz-mat suits. The air tight suits provided excellent protection against environmental hazards but were ineffective at stopping bullets or Rayne's blades. They possessed basic combat training.
- Jetpack Troopers - equipped with high power jetpacks and air filtering masks, the elite jetpack squads of G.G.G. were deployed during the assault on Castle Gaustadt as support units. Their main protection was their mobility, as the heavy protective coats, masks and steel helmets they wore were ineffective against weapons fire or cutting weapons. They usually carried submachineguns or automatic rifles into combat.
- G. Gosler - s a Nazi Officer who collaborated with Gegengeist Gruppe for the creation of the Unholy Mecha. He commanding officer of Superpanzer Mobile Division.
- Superpanzer Mobile Division - essentially a bipedal walking tank, these mobile armor were used in the assault on Castle Gaustadt. A squad of five were deployed to secure the castle's Cathedral. The tanks were powered by Diesel engines (as evidenced by the massive exhaust pipes), possessed incredibly heavy armor as well as a minigun, rocket launcher and twin grenade launchers.
- Unknown officer - is mysterious Nazi officer of G.G.G. Nothing is known about who this person is.
- Maraisreq - are large, arachnoid creatures that have over-run the city of Mortton, Louisiana. Their primary objective is to swallow people whole, then regurgitating the liquefied remains (somewhat similar to how an owl regurgitates).
- Queen of the Underworld - is the "mother" of the Maraisreq and is more powerful than the generic ones, due to the sheer size of the creature. She can produce other Maraisreq out of a hole in its abdomen and attack at medium range.
- Daemites - are parasitic/predatory creatures that were awakened by the Nazis as they were searching for Beliar's skull. Despite not having any limbs and essentially being serpents, they are capable of standing up the entire length of their narrow bodies, making it difficult to hit them with bullets.
- Hedrox the Infinite - an ancient and powerful vampire chieftain from New Guinea. He wants to become the ultimate immortal, but for that he needs Beliar's pieces.
- Feral Vampire - are ancient breed of vampires, who - cut off from the world in New Guinea - evolved into perfect killers. They fought for Hedrox the Infinite and they went with him in the Castle Gaustadt to find the heart of Beliar.
- Giant Bat - are a race of big winged bats with a skull-like head who lived in New Guinea.
- Beliar - is a powerful demon who once ruled Hell. He has a skeletal appearance, looking much like metal thorns with pieces of torn red flesh hanging from it.
- Generic enemies - Primarily thugs. Both males and females make up the ranks of the minions (both human and vampire). They are lightly armored and go down with ease. Often armed with either melee weapons (crowbars, axes, swords, guitars, etc.) or guns (pistols, sub-machine guns, shotguns and occasionally tripod-mounted heavy machine guns).
- Suicide Bombers - Used by the Kestrels and Slezz to do exactly what their name implies. They have a demolition timer strapped to their chests, which the detonate on getting close to Rayne. Aside from this, they are unarmed.
- Ninja - A tricky opponent, the Ninja are the followers of Ephemera. They move very fast, and are able to block Rayne's harpoon attack using their electrified swords. They also attack from a distance by throwing Shuriken. Much like Ephemera, they appear to be dressed in BDSM-style leather.
- Other Dhampir - were dhampir who wear black and red suits and the males use large scimitar-like swords. They also use dual guns. Another noticeable difference is that both males and females have heavy facial tattoos.
- Foreman - These are large, turned vampires that carry heavy hammers and wear aprons. They are found almost exclusively in industrial areas, notably the large "Wetworks" facility that forms the Shroud-producing tower. What makes them extremely dangerous is that many of their attacks will knock Rayne to the ground, allowing easy follow-up attacks.
- Brute - As their name suggests, they have a penchant for brute force and will attack other vampire minions if they get in their way. They have curved horns on their heads resembling those of a ram, which they use when charging head-first at Rayne.
- Bio-Armor - Rayne only encounters a handful of these, similar in most respects to Brutes, except that the Bio-Armor are tougher. Although they have no heads, they have no problem finding and attacking their enemies. Xerx's bio-mech suit is a much larger version of the Bio-Armor.
- Shadow Legion - A minor threat in most respects. Their speed and agility are daunting, but they are more susceptible to dismemberment than any other minion. The Shadow Legion wear masks with multiple lenses (possibly night vision goggles) and attack with ninja-like moves.
- Kagan Elites - Heavily armored and armed with a sword in one hand and a machine gun in the other. They only appear close to the end of the game.
- Flying Vampires - A group of big, winged demon-like Vampires who served Cult of Kagan.
- Unraveler - While in actuality a boss in its own right, the Unraveller is given no back story, and seems to be an indiscriminate killer, targeting minions as well as Rayne. It resembles a massive humanoid with long arms and legs, and attacks by spitting acid with enough force to throw enemies off their feet.
- Kagan - was a powerful vampire overlord. He is a very old vampire, his age being unknown, but he has been alive long enough to sire several offspring. Kagan became involved with a sect of Nazis called the Gegengeist Gruppe.
- Ephemera - is dressed in black leather, has pale skin and no visible eyes. She is a daughter of Kagan and Rayne's half-sister.
- Ferril - is a proud and arrogant vampire, particularly when it comes to her self-proclaimed status as "the fastest and strongest". She is a daughter of Kagan and Rayne's half-sister.
- Dariel Zerenski - He is a son of Kagan and Rayne's half-brother.
- Xerx Mephistopheles - is a sophisticated mad scientist who invented the shroud and created various high-tech weapons. He is a son of Kagan and Rayne's half-brother.
- Delinda - was a vampire daughter of Kagan and Rayne's half-sister. She lived in the West Indies. She had the ability to manipulate snakes in a certain manner.
- Kestrel - are a group of Asian dhampir assassins. She is a daughter of Kagan and Rayne's half-sister.
- Slezz - she was an ancient vampire from a bloodline of purebloods known as the Shakab which originated in Babylonia. She was at some point deeply enamored with Kagan and subsequently became his brood mother; nurturing his seed and bearing his children. She is a mother of ManCow that are used as food for the vampires.
- Blood Balloon - Plump creature wielding a hammer.
- Crab Puncher - A mechanical monstrosity.
- Crimson Demon - Reconstituted blood monster.
- Elite Guard - Elite warrior for kagan, wielding a sungun and a big sword.
- Flying Parasite - Swarming little insects, full of blood.
- Frog Man - Leech-like creature with electrical attacks.
- Kagan - Father of Rayne, and leader of vampires.
- Meat Spike - Meaty spike that grows out of the ground and explodes.
- Shambler - Slow moving creature, only killable with sunlighgt.
- Tosser - Vampire engineer, who throws explosives.
- Vamp Lady - Lady vampire who tosses sharp fans.
- Vamp Punk - Vampire with a rapier and a gun.
- Wraith - A ghostlike creature.
- Wheeler - Fast creature who has blades for hands.
- Zeta Gamma - A load-bearing demon.
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