As the highly anticipated science fair gets underway, Wednesday Addams prepares to showcase her revolutionary experiment involving the genetic code of her beloved pet squid, Socrates. Her goal? To usher in a new era of human enhancement. However, her ambitious endeavor comes with an unexpected consequence: Uncle Fester starts to undergo a transformation. Just as she is about to bask in the glory of her achievement, Wednesday is startled by the sudden appearance of her family at the event. Her invention piques the interest of the brilliant scientist Cyrus Strange, who recognizes Wednesday's extraordinary talents. Meanwhile, at the Addams' spooky mansion, Gomez grows increasingly anxious about the growing distance between himself, Morticia, and their children, prompting him to organize a family vacation to strengthen their bond.
As the family hits the road, they are approached by a lawyer named Mr. Mustela, who whispers unsettling allegations that Wednesday might have been switched at birth and could be a non-Addams. While Gomez and Morticia dismiss his claims, doubt begins to seep into their minds. The family embarks on a cross-country adventure, led unknowingly by Fester, who is affected by Wednesday’s experiment, as they head toward Niagara Falls instead of their intended destination of Salem, Massachusetts. During their stop in Sleepy Hollow, Gomez and Morticia can’t shake off Mustela's ominous assertions, amplifying their concerns over Wednesday's true lineage.
Arriving in Miami, seeking counsel from Cousin Itt, Fester shares a revealing story about visiting the delivery room during Wednesday's birth, which only heightens Gomez and Morticia's anxieties. Journeying through San Antonio, they bid farewell to Itt at the Grand Canyon. Meanwhile, Wednesday, having sensed Mustela's ulterior motives, ensnares him in a trap and learns he works for none other than Cyrus. The shocking revelation comes to light: he may actually be her biological father. Conducting a DNA test using Gomez's hair, she finds what appears to be confirmation of her fears, leading her to make the painful decision to leave her family behind while they sleep.
Upon waking to find Wednesday gone, the Addams family springs into action, chasing her to Sausalito, California. There, Cyrus welcomes Wednesday into his quirky abode and presents her with a revolutionary formula that produces human-animal hybrids, coincidentally similar to her own creation. Intrigued, she is drawn deeper into the eccentric doctor’s world. However, chaos erupts with the arrival of her family, leading Wednesday to heed Cyrus's request to delay her departure.
As Pugsley discovers the disconcerting truth that Ophelia, Cyrus's daughter, has transformed into a pig, the sinister motives of the doctor come to light. He reveals that he has been using Wednesday's formula for his own dark ends, taking the Addams family captive. When Morticia refuses to comply with Cyrus's twisted demands, he seeks the help of Pongo to track down his prized hybrid. Unbeknownst to him, Lurch and Pongo share a strange connection from their past, having met in a psychiatric institution. This shared history inspires a unique partnership as they team up to rescue the family.
Amid the chaotic confrontation, Cyrus inadvertently succumbs to his own creation, turning into a grotesque hybrid beast blending a chicken, cow, goat, and pig. In a wild turn of events, he attempts to eliminate the family, but Fester, now transformed into a squid-like creature, intervenes. As the two monstrous foes clash, Cyrus meets his demise when he falls off a cliff. Fortunately, Wednesday manages to restore Fester to his original form using a pendant blessed with the blood of her ancestors, a gift from Morticia.
With the family back together and safe, Wednesday returns home alongside Pongo and the newly humanized Ophelia, who has developed a crush on Pugsley, delighting their peculiar family. In a surprising twist, Gomez confesses he wears a toupee due to a past napalm mishap that caused him to lose his hair. He reassures everyone that their next journey will be an epic adventure around the globe.
