Maika Monroe, already a genre darling thanks to “The Guest,” “It Follows” and “Watcher,” delivers her best turn yet as rookie FBI agent Lee Harker, a watchful loner whose uncanny intuition for rooting out perps — or is it some kind of evil ESP? — lands her a special assignment tracking an elusive suspect dubbed the Longlegs Killer.

So named for the cryptic signed notes left at a string of grisly murder-suicides rocking the rural Pacific Northwest, Longlegs is an enigma: a serial killer responsible for turning family men violently on their wives and children, despite no evidence that he was ever there. Monroe infuses Lee with a bone-deep introversion, down to the way she stiffly moves through her bleak world, more at ease with gruesome crime scene photos and occult symbols than she is around people.

Echoes of “Se7en,” “Zodiac” and especially “Silence of the Lambs” position Lee as the Clarice Starling of this piece, in which hallucinogenic editing by Greg Ng and Graham Fortin, cinematographer Andres Arochi’s diabolically patient camera work, and jarring sound design by Eugenio Battaglia combine to conjure potent menace in the jump scares, nightmare images and ominous negative spaces of the frame.

But something more insidious begins percolating in Perkins’s slice of American Gothic horror once Lee’s quarry turns hunter and her mind tugs at a long-buried childhood memory of a ghoulish stranger with a singsong voice, remembered only in snatches. And once you get a full gander at Longlegs, well, good luck getting him out of your head, too.

Perkins initially wields Nicolas Cage’s most unhinged role to date with restraint, the actor’s nearly unrecognizable features cropped just enough out of frame to send the imagination skittering. When he’s eventually unleashed, unnaturally pallid, powdered and plumped under wild hair and grotesque facial prostheses, it’s to skin-crawling effect. Who knew that the secret to a maniacal all-timer of a Cage role was giving his mothballed boogeyman a botched makeover and an over-the-top obsession with ’70s glam rock, then keeping his battiness strategically at bay? (You’ll never hear T. Rex’s “Get It On” the same way.)

Cage cranks the dial, sealing his Longlegs as one of the great horror villains. Monroe, meanwhile, holds the center of the slow-burn chiller opposite Lee’s religious hoarder mother (a fantastic, unpredictable Alicia Witt) and her amiable boss, Agent Carter (Blair Underwood). But it’s the deliciously strange interaction with Longlegs’ only known survivor (a mesmerizing Kiernan Shipka, star of Perkins’s 2015 debut “The Blackcoat’s Daughter”) that highlights the final stretch of the movie’s descent into the unexpected, even if the lore takes a few unconvincing late-breaking turns to get there.

Still, Perkins, who made his own acting debut portraying the younger version of his father Anthony in 1983’s “Psycho II,” knows the terror of unmooring us from our places of safety, including the safety we search for in nostalgia and in the stories we tell ourselves. Playing with aspect ratio and composition with a sure hand, the filmmaker blankets his fourth feature in an unsettling shroud of wrongness as Cage and Monroe play out their unorthodox cat-and-mouse game. Even the end credits are cleverly designed to ensure viewers linger in a state of visceral unease, letting the dread sink in.

R. At area theaters. Contains bloody violence, disturbing images, language, satanic panic and Nicolas Cage rage. 101 minutes.