The movie kicks off with Sandy Cheeks stepping out of her treedome, accompanied by her mechanical horse Sparky, as she collects valuable data on the inhabitants of Bikini Bottom while singing a cheerful tune. Meanwhile, SpongeBob is attempting to refine his jellyfishing skills in front of Sandy until a massive claw suddenly emerges, snatching Bikini Bottom from its watery home, igniting panic among the residents. Distraught at the thought of losing Gary, SpongeBob finds himself heartbroken, especially with Sparkys' rear being taken too. With determination, Sandy pulls out her goggles to zoom in on the claw and discovers that it belongs to B.O.O.T.S. Marine Biology Lab in Galveston, Texas. This place holds significance for her as she once worked there, stirring her curiosity about what is happening. In an attempt to reach her friends, Phoebe and Kyle, she finds herself interrupted by an advertisement for Gushing Waters water park, revealing that the park was established by Sue Nahmee, before the call gets cut off.
Determined to retrieve Bikini Bottom, Sandy declares her intention to travel to Texas with SpongeBob. She devises a plan, leading them to ride clam shells through a volcanic vent to reach Texas Airlines Flight 10:35, leaving Sparky back. After 14 long hours, they find themselves flying over Galveston, but Sandy accidentally kicks SpongeBob off the wing, only to catch him mid-air and glide gracefully, revealing her true identity as a flying squirrel. As they make an attempt to land at the water park, they're unexpectedly engulfed by a tornado, causing a rough crash landing with SpongeBob ending up atop a cactus. Overcome by dehydration, Sandy kindly offers him water from another cactus while examining a nearby license plate that reveals they are a staggering 626 miles away from their intended destination. Thus, they embark on foot.
Meanwhile, back at the lab, chaos ensues at the Krusty Krab. Mr. Krabs decides that Squidward should investigate the commotion outside, but after some initial hesitance, he ends up returning in a fit of fright after encountering Gary and Patrick. Phoebe and Kyle are at the computer, uncovering that SpongeBob and Sandy are indeed missing. Sue enters with her pet dog Cuda, demanding to know who is unaccounted for.
In the arid Texan landscape, Sandy and SpongeBob come across a menacing group of Stetson-clad rattlesnakes who attempt to devour them. But armed with her karate skills, Sandy courageously defends them, only to be bitten on the foot, causing her to puff up like a balloon. As danger looms, she whistles for help, and an RV filled with her relatives arrives, clarifying they are a family circus. They quickly deal with the snakes, and Sandy's mother deflates her back to normal before announcing their determination to assist in retrieving Bikini Bottom.
In the lab, Sue brutally shakes the glass dome enclosures before revealing her sinister ambition to create sea pals by genetically modifying fish into air-breathing beings through a complex procedure involving gene machines. Meanwhile, SpongeBob has a bonding moment with Randy, Sandy’s brother, while learning to fix the RV's engine, and as the day breaks, Sandy admires posters of her family's special acts while cooking breakfast. The family enjoys a hearty meal, highlighting Ma Cheeks' aspirations for Sandy.
With mischief brewing in the dome, Plankton shares his plans of cloning himself into a powerful army. Meanwhile, the residents of Bikini Bottom are offered free Genetic Modification Paste, leading to some precarious situations as Phoebe and Kyle capture Squidward, Mr. Krabs, and Patrick to subject them to the gene machine. Squidward soon finds himself trapped by Sue and questioned by the now arriving kids, as chaos unfolds.
In the midst of it all, SpongeBob seeks guidance in mastering the Cheeks' family whistle from Randy, but soon they are pursued by law enforcement over stolen goods in the RV. The thrill escalates as they are swept up by a tornado again. With Sandy's quick thinking and skills, she deftly saves the situation, landing them merely eight miles from Galveston. They must decide how to reach the Water Park, ultimately resorting to a cannon launch without parachutes, with Sandy using her gliding skills to finally arrive at the water park just outside the lab.
As the pursuit continues, Sandy carefully scans the area for signs of the lab while SpongeBob finds amusement in tickling everyone’s feet. However, they’re soon discovered by Cuda, plunging them down a water slide. At the top, Sandy spots the B.O.O.T.S. Laboratory and takes flight, while Cuda's relentless pursuit adds to the excitement. They cleverly evade capture through drainage pipes, but SpongeBob's eagerness leads him right to Phoebe and Kyle, while Sandy gets trapped by Sue in a cage.
Confronted by her former acquaintances, Sandy learns that their loyalty to Sue stems from the allure of getting something as mundane as an empty vending machine filled, showcasing the irony in their choices. At the lab, SpongeBob is placed in a mini roller coaster heading for the cloning machine, and Sue narrates her tragic tale of losing her humanity to a Piranha, revealing her true self as an evil robot.
In a climactic moment, Sandy, feeling overwhelmed, takes a stand on the hamster wheel, urging everyone else to assist. As the mini SpongeBobs are created within the cloning machine, one encourages Sandy not to lose faith in retrieving Bikini Bottom. Recognizing her second family in the Bikini Bottom residents, Sandy manages to rally a spirited resistance against Sue through the combined efforts of everyone involved. Ultimately, they create an electric charge to shoot the dome back into the ocean, successfully restoring Bikini Bottom while positioning Sparky appropriately.
Ultimately, the Krusty Krab transforms into a vibrant circus tent where the Cheeks family entertains the crowd with their talents. Amidst the festivities, Mr. Krabs serves his innovative Texas-style Krabby Patties, capturing the playful essence of their reunion. The film closes with Sandy, proudly riding Sparky, singing about the love and belonging she feels between her two homes—Bikini Bottom and Texas—and her commitment to doing good, with Sue amusingly transformed into a fish, completing the story.
