NOTE: This spoiler was submitted by Jeremy

The film opens in New York City. Tom Cat is making his way to the park while Jerry Mouse meets with a shady rat for a place to stay. After having no luck, Jerry comes across Tom in Central Park pretending to be blind while playing the piano for money to a crowd of onlookers. Jerry sabotages the act by dancing for the crowd, stealing Tom’s money. Tom goes after Jerry, revealing his non-blindness to the angry crowd. The cat chases the mouse until Tom crashes into a young woman, Kayla Forester (Chloe Grace Moretz), ruining her delivery of clothing. After an argument with her boss, Kayla quits her job.

Tom catches Jerry running into the Royal Gate Hotel, but the doorman boots Tom out, leaving Jerry to sneak into the hotel undetected. Kayla goes in to grab a snack before spotting a woman, Linda Perrybottom (Camilla Arfwedson), awaiting an interview. Kayla pretends to be part of the staff and convinces Linda to give her her resume before saying the hotel is looking for someone more local. Kayla passes the resume off as her own and manages to score a meeting with the hotel manager, Mr. Henry DuBros (Rob Delaney), and events manager, Terence Mendoza (Michael Pena), who hire her for the weekend since the hotel is hosting a wedding for a wealthy couple.

Tom tries to find a way into the hotel but runs into an alley cat gang led by Butch (Nicky Jam). When they threaten Tom, he manages to call an animal control officer in their direction, causing them to run away. Meanwhile, Jerry gets himself comfortable in his own little room within the walls of the hotel.

Terence takes Kayla on a tour of the hotel and the people who work there before the bride and groom, Preeta (Pallavi Sharda) and Ben (Colin Jost), arrive with their pets, Spike the dog (Bobby Cannavale) and Toots the cat. Spike barks in Jerry’s direction until he feeds Spike a dog treat. Jerry’s presence is made known, and Kayla vows to catch the mouse before Preeta and Ben find out about him and decide to take their wedding elsewhere. She befriends the hotel’s bartender, Cameron (Jordan Bolger), in her attempts to catch Jerry, but after she sets a mousetrap with some cheese to lure him there, the mouse catches on quickly and takes the cheese without setting off the trap and leaves a note and tip for Kayla. She realizes she has found herself a challenge.

That night, Tom is trying to play his broken keyboard in the rain until he sees Jerry from a window in the hotel room. After talking to his shoulder angel and devil (both played by Lil Rel Howery), Tom resolves to go after his rival. He makes several attempts to make it into the room, all of which are foiled by Jerry and lead to Tom getting injured repeatedly. He eventually opens the window himself and chases Jerry through the room, both of them trashing the place until Kayla hears the commotion and finds Tom, recognizing him from earlier. Before she can kick him out, Tom manages to communicate with her and say he can help her catch Jerry. She takes Tom to DuBros and Terence to suggest that they hire him briefly to help catch Jerry instead of an exterminator who can cause problems for the wedding. Although Terence doesn’t like the idea, DuBros likes Kayla’s initiative and agrees with her.

Tom starts his job of going after Jerry when he spots the mouse in the halls, but when he tries to beat him with a bat, he ends up hitting Spike, making a new enemy in the process. Kayla gets help from the bellhop, Joy (Patsy Ferran), who noticed the tiny door in the hall that leads to Jerry’s room. Kayla formally meets Jerry when he gives her his business card, but once he spots Tom, the two continue their shenanigans, leading Tom to smash face-first into the wall when Jerry moves the door to the right.

Kayla and Terence go to Ben and Preeta’s room, where Ben talks about bringing in elephants for the wedding to carry him and Preeta, although she thinks it’s too much. After Ben and Terence leave the room, Preeta confides to Kayla that her engagement ring is missing, and she is afraid of Ben finding out. When Ben notices it’s not on her finger, Kayla covers for her and says she is getting it cleaned. In reality, Jerry has it in his room. Terence is also made to take Spike out for a walk, and the dog causes problems for him.

Tom comes up with an elaborate Rube Goldberg device to trap Jerry in a cage after luring him out with cheese. He brings Jerry to Kayla as proof and then ships him off somewhere. While Kayla has her own little celebration, Tom goes to play the piano until Toots catches his eye. He starts to play a song until Jerry returns and messes with him. Kayla catches them and stops them from causing trouble, but after she threatens to bring in exterminators, Jerry reveals he has Preeta’s ring and will give it back as long as he can stay in the hotel. Terence comes back with Spike, and he notices Jerry in Kayla’s pocket. Before he can find the mouse, Spike chases after Tom and Jerry, causing a major commotion in the lobby that ends when they cause the ceiling to collapse. Kayla ends up grabbing the ring so she can return it to Preeta.

Terence tells DuBros he should fire Kayla for failing to catch Jerry since he spotted him during the commotion, but DuBros thinks the wedding planning is stressing Terence out, so he puts him on leave and promotes Kayla to his position. She goes to the roof to find Tom and Jerry and tells them they can stay in the hotel as long as they can prove they can get along without causing any more damage since the wedding is the next day.

Kayla sends Tom and Jerry out into the city for some time together while she gets the staff ready for the wedding. The two enjoy themselves, even though Tom (naturally) takes a lot of hits on the streets. After the elephants arrive, Kayla meets with Preeta, who admits that she and Ben haven’t been communicating well enough, and she hasn’t been able to bring herself to tell him that he has done too much for the wedding, fearing it will be a disaster. Kayla also runs into Ben, who expresses similar sentiments, but Kayla knows that the two of them really do love and care for each other. Unfortunately, Ben misinterprets Kayla’s advice as to go even bigger than he is already.

After an incident at a baseball game, Tom and Jerry are taken to the animal pound where they find Butch and his gang (as well as Droopy Dog dressed like Hannibal Lecter). They dare Tom to eat Jerry to prove that they aren’t actually friends, and after Tom puts Jerry in his mouth, the mouse lights a fire in there that blows their cover. Fortunately, they are bailed out by Terence. Unfortunately, he gets them in separate rooms to spread lies about each other to keep them turned against one another.

Terence leads the duo to go to the hotel separately as the wedding is starting to take place. He gets Tom to go after Jerry, chasing him on top of the wedding cake. Chef Jackie (Ken Jeong) starts hitting the cake to get Jerry, leading him to fly towards the elephants, who promptly freak out at the sight of Jerry. This causes them to start stampeding throughout the hotel before they end up running into the streets. Following the disaster, Preeta tells Ben the wedding is off and gives him back the ring. Kayla is then forced to come clean to DuBros about lying about her resume and sees herself out of the hotel before she is officially fired.

Tom and Jerry realize it was their fault the wedding was ruined, and they finally decide to set aside their differences to help Kayla. They find her and Jordan in the market and offer their services to help put on a wedding in Central Park. Kayla finds out that Preeta is heading for JFK Airport, so she has Tom and Jerry chase after her on a remote-controlled skateboard with a drone to grab Toots and have Preeta’s car turn around to chase her. Meanwhile, Kayla talks to DuBros and apologizes for lying, but he is convinced that she is capable of turning things around, even as Terence argues. However, Kayla knows Terence set Tom and Jerry loose to fight, and she promises to keep it a secret if he helps her out, which he agrees to. Kayla gets Ben and everyone to the park, where Preeta arrives and finds everyone. She and Ben reconcile and are finally married.

During the reception, Kayla and Terence make amends, and Kayla is allowed to keep her job. She does bring Linda back so that she can have the job she deserves. Tom is playing the piano for Toots again until Jerry starts to mess with him again, leading them to also run into Spike. The trio pulls down the “The End” curtain for the humans so that they can continue their mayhem at a safe distance.

After the credits, Ben receives a bill for both weddings, to which DuBros said that it doesn’t look good for him.

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Long-time rivals Tom and Jerry find themselves in New York City at the Royal Gate Hotel. When a young woman named Kayla Forester secures a job there after stealing another woman's resume, she finds that the cat and mouse can cause problems for a wedding that weekend for rich couple Ben and Preeta. Kayla gets Tom's help to catch Jerry before the wedding is ruined. Meanwhile, events manager Terence Mendoza is suspicious of Kayla.

Tom and Jerry engage in their usual antics, even getting Spike the dog in on it. When Kayla gets Terence's job after manager DuBros thinks he is stressing out, she asks the duo to keep it cool for the wedding if they want to stay. During the preparation for the wedding, Kayla learns that while Preeta and Ben really do love each other, she thinks all that Ben is doing for the wedding (like booking elephants to carry them) is too much.

Tom and Jerry start to get along until they are taken to the animal pound for disrupting a baseball game. Terence bails them out but manipulates them into hating each other again before sending them back to the hotel where they ruin the wedding with their shenanigans. Preeta calls off the wedding while Kayla must come clean to DuBros about her lies, so she quits.

Realizing it was their fault things went wrong, Tom and Jerry bury the hatchet and resolve to help Kayla save the wedding. They all work together to get everyone to Central Park for an impromptu wedding. Ben and Preeta reconcile and get married, while Kayla is allowed to keep her job. However, Tom and Jerry continue doing what they do best - fighting each other.