The film is set in the heart of Transylvania and the story appears to take place sometime during the mid-19th Century. Professor Abronsius, formerly of the University of Königsberg and his apprentice Alfred are on the hunt for vampires. Abronsius is old and withering and barely able to survive the cold ride through the wintry forests, while Alfred is bumbling and introverted. The two hunters come to a small Eastern European town seemingly at the end of a long search for signs of vampires. The two stay at a local inn full of angst-ridden townspeople who perform strange rituals to fend off an unseen evil.
In the aftermath of the death of Dracula's wife Martha (Jackie Sandler) at the hands of an angry mob, Count Dracula (Adam Sandler) designs and builds a massive five-star hotel in Transylvania in which to raise his daughter Mavis (Selena Gomez) and to serve as a getaway for all the world's monsters.
For generations, a secret war has been waged between vampires and Lycans, an ancient species of werewolf. Selene, a Death Dealer, a vampire specialized in assassinating Lycans, tracks two Lycans. Selene's motivation goes beyond duty; she also wants revenge because, 600 years ago when she was a child, Lycans slaughtered her family. The vampires believe they defeated the werewolves many centuries ago and killed their leader, Lucian, and that they must kill the surviving Lycans. Selene locates the Lycans' den and learns they have developed a new kind of bullet capable of killing the vampires.
As the film opens, a young man (John Amplas), travelling on an overnight train from Indianapolis to Pittsburgh, sedates a young woman with a syringe full of narcotics, slices her wrist with a razor blade, and drinks her blood. The next morning, he is met at the Pittsburgh train station by a mysterious man in white (Lincoln Maazel) who escorts him away, whereupon the pair board a local train destined for Braddock.
Renfield, a solicitor, makes a journey into Transylvania via stagecoach. He mentions his destination, Castle Dracula, to the locals who react with alarm. They tell him Count Dracula is a vampire and when he doesn't believe them, one insists he wear a cross. When he arrives at the Castle, the Count bids him welcome. After drinking drugged wine, Renfield drops the cross and is bitten.
While walking her guard rounds in the country, 17-year-old Doris Lang, the daughter of a deceased werewolf hunter, is attacked by Count Magnus Lee, a 10,000-year-old, long-lost vampire lord (also known as a Noble), who intends to make her his new vampire bride.
The film starts with Bold Cheung having a nightmare about ghosts.
Bold Cheung is challenged to spend the night in an abandoned house where he must peel an apple in front of a mirror. If he breaks the skin then something bad will happen. Upholding his mantle as the boldest he accepts. However, that night whilst peeling the apple his friends trick him. Whilst scolding his friend for the prank a real ghost appears and snatches Cheung's friend away. The ghost reaches for Cheung but he cuts its hand off and then quickly shattering the mirror, causing the house to collapse.
The prologue shows a church in Guatemala in which a man and a boy, Ben Mears and Mark Petrie, are filling small bottles with holy water. When one of the bottles begins to emit an eerie supernatural glow, Mears tells Petrie "They've found us again." Knowing an evil presence is there, they decide to fight it.
The film is about a woman who experiences frightening visions after visiting an insane asylum where one of the inmates claims to be Count Dracula (here following the Hungarian spelling Drakula). She has trouble determining whether the inmate's visions are real or merely nightmares.
One night, Caleb Colton (Adrian Pasdar), a young man in a small town, meets an attractive young drifter named Mae (Jenny Wright). Just before sunrise, she bites him on the neck then runs off. The rising sun causes Caleb's flesh to begin to burn. Mae comes with a group of roaming vampires and takes him away. The most unsociable of all the vampires, the callous and sociopathic Severen (Bill Paxton), wants to kill Caleb, but Mae reveals she has turned him into a vampire. Their charismatic leader, Jesse Hooker (Lance Henriksen), reluctantly agrees to allow Caleb to remain with them for a week to see if he can learn to hunt and become a trusted member of their group. Caleb is unwilling to kill to feed, which alienates him from the others. To protect him, Mae kills for him and then has him drink from her wrist. After Caleb endangers himself to help them during a daylight police raid on their motel, Jesse and the others are temporarily mollified.
A young, hardworking Iranian man named Arash lives with and takes care of his heroin addicted father, Hossein. They are harassed by a cruel, drug-dealer pimp named Saeed, who seizes the young man’s prized car in exchange for money the father owes him. In a crime of opportunity, Arash steals a pair of diamond earrings from the wealthy young woman he works for. The pimp comes across a strange, young woman in a chador at night, and back at his apartment she grows long fangs and goes for his neck. As she leaves she passes by the young man, who has come to offer the earrings for his car. He finds the drug dealer dead, taking back his car keys, along with the drugs and cash. The young man dresses up as Dracula, and goes to a night club where he is seduced into taking one of the “X” pills he is selling by a young woman he knows. Under the influence, he is rejected by her, and ends up lost at night on the street.
In 1921, German director Frederich Wilhelm Murnau takes his cast and crew on-location in Czechoslovakia to shoot Nosferatu, an unauthorized version of Bram Stoker's novel Dracula. Murnau keeps his team in the dark about their schedule and the actor playing the vampire Count Orlok. It is left to the film's other main actor, Gustav von Wangenheim, to explain that the lead is an obscure German theater performer named Max Schreck, who is a character actor. To involve himself fully in his role, Schreck will only appear amongst the cast and crew in makeup, and will never break character.
The Monster Squad is a society of young pre-teens who idolize classic monsters and monster movies and hold their meetings in a tree clubhouse. Club leader Sean (Andre Gower), whose five-year-old sister Phoebe (Ashley Bank) desperately wants to join the club, is given the diary of legendary monster hunter Dr. Abraham Van Helsing (Jack Gwillim), but his excitement abates when he finds it is written in German. Sean, his best friend Patrick (Robby Kiger), and the rest of the Monster Squad visit an elderly man, known as the "Scary German Guy" (Leonardo Cimino), actually a kind gentleman, to translate the diary. When the Monster Squad wonders how the German man is so knowledgeable about Van Helsing's battle with monsters, he wryly comments that "he has some experience with monsters" and his shirt sleeve briefly reveals a Concentration camp number tattoo.