In the aftermath of the catastrophic events triggered by Re-Animator, doctors Herbert West and Dan Cain find themselves entrenched in a violent Peruvian civil war, which surprisingly offers them the freedom to delve further into West's controversial reanimation serum. Amidst the surrounding turmoil, they capitalize on the overwhelming casualties, utilizing them as subjects for their experimental pursuits. After a life-threatening encounter with enemy forces, the pair manage to escape back to Arkham, Massachusetts, where they reclaim their positions as medical practitioners at Miskatonic University Hospital. There, West’s obsession pulls him back into his illegal experiments, this time operating clandestinely in Cain's basement laboratory.
By scavenging body parts from the hospital’s morgue and nearby graveyard, West makes a revolutionary breakthrough—his reagent has the ability to revive individual body parts! His ambition grows as he becomes consumed with the idea of assembling a brand new being from these disparate parts. However, his fixation sharpens when he discovers the heart of Megan Halsey, Cain's beloved fiancée, within the morgue. Swearing to incorporate her heart in his ambitious project, West successfully persuades Cain to embark on this perilous journey alongside him. As their preparations unfold, they stumble upon evidence of the notorious Miskatonic Massacre, including the disembodied head of Dr. Carl Hill preserved in the morgue.
Meanwhile, pathologist Dr. Wilbur Graves unearths a vial of West's reagent along with Hill's head while investigating the massacre's aftermath. Seizing the opportunity, Graves reanimates Hill's severed head, setting off a string of events that will prove disastrous.
As tensions rise, police officer Lt. Leslie Chapham starts his inquiry into West and Cain, the only survivors of the tragic massacre. The gruesome truth looms large over them as Chapham hints that West's experiments might have played a role in the dreadful incident that led to the reanimation of his wife as a mindless zombie. When Chapham confronts them, he is met with hostility; this soon results in his untimely demise at the hands of West, who employs a cloth infused with a lethal agent to end his life.
In a twist of fate, West then resurrects Chapham, planning to conceal his heinous act. However, the reanimated officer, now erratic and violent, stumbles out into the adjacent cemetery. Dr. Hill, fueled by revenge, manipulates Chapham through his psychic abilities and orders him to restore mobility to his own head by compelling Dr. Graves to affix bat wings to his neck. Hill's influence swiftly extends to the other undead victims of the Miskatonic Massacre, paving the way for an impending catastrophe.
As Gloria's life force slips away, West secures the last essential component for his audacious experiment—her hauntingly beautiful visage. With Megan's body finally assembled, he and Cain inject the innovative re-agent into her heart, anxiously awaiting the transformative magic that could unfold. Suddenly, a foreboding delivery arrives at their doorstep—Dr. Hill's head, sporting its newly acquired wings, begins to hover ominously. Meanwhile, Hill's legion of undead minions charge into their home, compelling West to retreat to the sanctuary of his underground laboratory.
There, an intense confrontation erupts between the newly reanimated "Bride" and Cain's current lover, Francesca Danelli, an Italian journalist whose prior escapades in Peru have led her to this grim locale. As Cain turns away from the Bride in favor of Francesca, her heart shatters, quite literally resonating her anguish. In a frantic attempt to reclaim her lost desire, the Bride violently extracts Megan’s heart from her own chest, leading to her disintegration into a remnant of flesh.
As Hill and his grotesque followers bear down on West, Cain, and Francesca, they find themselves fleeing through the lab's decaying walls and ultimately seeking refuge in a forgotten crypt within the adjacent graveyard. Here, West's earlier experimental subjects groan to life, instinctively shuffling towards him, their advance only halted by West's formidable presence. Just as the crypt teeters on the brink of collapse, it crashes down, entrapping Hill, West, and the horde of zombies. Cain and Francesca, however, manage to escape the debris, clawing their way back to the surface, hand in hand. In the eerie aftermath, the heart of Megan, still held in the lifeless remains of the Bride, falters and ultimately ceases to beat, echoing the chaos that enveloped them.
