Professor Jeffries, Alfred Molina (voice), hires a Sherpa guide named Pemba Shepra, James Sie (voice), to help him in his quest to locate the legendary Shangri-La. Pemba grows reluctant, fearing they are intruding on the Yeti’s territory, but Jeffries remains undeterred and presses on alone. The expedition is soon halted when the two are attacked by the mysterious monster, a chilling reminder of what guards the hidden valley.
In Paris, Mystery Inc.—Fred Jones, Frank Welker (voice); Daphne Blake, Grey DeLisle (voice); and Velma Dinkley, Mindy Cohn (voice)—try to enjoy a vacation, only to discover that Shaggy Rogers, Casey Kasem (voice), and Scooby-Doo, Frank Welker (voice), are late. The pair accidentally boards the wrong plane and winds up in the Himalayas alongside Alphonse LaFleur, René Auberjonois (voice), a French-Canadian hunter who plans to kill the Yeti and uses them as bait. A quick phone call from Shaggy helps Fred pinpoint their location, and he guides the women toward a rescue mission using the plane’s GPS.
Meanwhile, Shaggy, Scooby, and LaFleur reach a small, nearly abandoned mountain village where they encounter Jeffries and Pemba, who have recently escaped the Yeti. The High Lama, James Hong (voice), reveals a nearby weather station and shows them a large crystal that he believes protects the village from the Yeti’s wrath. Jeffries becomes obsessed with the crystal, while Pemba’s sister Minga, Kim Mai Guest (voice), joins the group after realizing she has a crush on the station’s radio DJ, who moonlights as a broadcaster.
As a snowstorm approaches, the group makes camp. Jeffries secretly leaves with explosives, hoping to mine more crystals. The Yeti attacks Shaggy and Scooby; LaFleur’s attempt to capture it backfires, and the friends become separated in the worsening weather until Dell Chillman, Jeff Bennett (voice), an acquaintance and amateur cryptozoologist they met at Loch Ness, arrives to rescue them and brings them to the station.
Back with Mystery Inc., the team reaches the village and tracks Jeffries and Pemba, but there is no sign of Minga or the missing scientist. They split up to search, and Chillman heads off with Shaggy and Scooby to continue the search. The Yeti attacks again, and LaFleur reappears to save them but falls off a cliff, presumed dead. In a narrow escape, Shaggy and Scooby stumble onto Shangri-La itself, only to be confronted by the Yeti once more.
Chillman eventually finds the others and learns his station has been destroyed and the helium tanks stolen. The groups reunite in an old mine, where they discover Jeffries mining the crystals with renewed intensity. They confront him; he denies being the monster, but the Yeti attacks the group, forcing a rapid retreat. Jeffries breaks free and tries to haul away the crystals, but a trap Mystery Inc. set catches him, and an explosion triggers an avalanche.
In the ensuing chaos, the Yeti rescues Velma and Chillman, and it’s revealed that Minga had disguised herself as the Yeti to keep Chillman from ending his radio show and to confess her feelings for him. She also stole the helium tanks to help her move up and down the mountain more easily.
With the danger resolved, Jeffries is arrested for illegal mining; LaFleur is rescued and returned to the village by a mysterious entity; and Chillman and Minga begin a relationship, joining Mystery Inc. as they attempt to return to Paris, only to learn that Fred has somehow ended up in the Amazon and is set on reuniting the team.
