JJ, a veteran CIA agent, reunites with his protégé Sophie, in order to prevent a catastrophic nuclear scheme threatening Vatican City, which disrupts a high school choir trip to Italy.
JJ, Sophie, and Kate have relocated to Langley, Virginia, since the events of the first film. In addition to managing field agents and baking, JJ has accepted a desk job as a CIA analyst, where she also trains Sophie to be an agent. Now a teenager in high school, Sophie has begun to grow impatient with JJ's incessant training. Sophie does not recognize JJ as her father, even though he is married to Kate and serves as a father figure to her.
One day, JJ leads Christina on an intelligence collection expedition. Christina is able to obtain the information, which includes the location of more than 100 suitcases in Europe that contain WMDs from the Soviet era. However, a spy ambushes Christina as she gets ready to return to Langley, stealing her car before murdering her. Sophie finds out that her high school choir has been selected to perform at a G7 event in Italy following a day of training with JJ. Along with Sophie's best friend Collin, Sophie's crush Ryan, and Nancy, the vice principal of the high school, JJ goes with Sophie to chaperons the trip. Although he has not disclosed to Collin that he is a CIA agent, David Kim permits JJ to accompany him on the trip because he is Collin's father. Collin is informed by Sophie that she intends to ask Ryan out to the homecoming dance and have a romantic moment with him.
Throughout the trip, JJ attempts to appear like a cool parent while simultaneously being a responsible chaperons in Nancy's eyes. Sophie, Collin, and Ryan slink out while in Florence. Even though JJ catches them, he lets them leave as long as they return before curfew. Collin is abducted while assisting Sophie in making an impression on Ryan. Sophie learns of the kidnapping and makes an unsuccessful attempt to find the parent. The kidnapper is identified by JJ as Simon Crane, who murdered JJ's entire army unit. In order to save his son, Crane's boss calls David and instructs him to travel to Rome without telling the CIA. Soon after, JJ gets in touch with David and consents to meet him there.
The kidnapper wants the codes to the suitcase WMDs on a military base in Anzio, JJ and Sophie discover when they meet David and Bobbi in Rome. They require access to a van and some equipment in an MI6 safe house in order to obtain the codes. JJ and David enter covertly, but as they do so, they unintentionally let loose a cage of parakeets, which attack them mercilessly. By pretending to be David's wife, stepbrother, and stepdaughter, respectively, Bobbi, JJ, and Sophie are able to get the four of them onto the military base in Anzio the following day. While JJ is engaged in a boxing match, Sophie and Bobbi obtain the WMD's pass codes by hacking the base's server. CIA agent Connelly returns to Langley and discovers that not only did Christina fail to show up for her rendezvous, but that JJ, Bobbi, and David also downloaded the pass codes, which makes him think that they have gone rogue.
When JJ and David attempt to meet the kidnappers, Crane ambushes them, and they are abducted as well. JJ and David discover that Nancy, Crane's boss, is the one who provided the CIA with the anonymous tip regarding the WMD intelligence. Nancy knew that the only way to isolate David would be to kidnap Collin after bribing the committee that chose the school's choir. In order to obtain insurance, Nancy persuades David to give her the codes, after which she instructs Crane to go kill Collin. JJ is rescued by Sophie and Bobbi after Sophie manages to locate his phone. They pursue Crane and save Collin, but Crane manages to get away. Collin learns the truth about his father from Sophie while Bobbi searches for Nancy and Crane. While Sophie has a crush on Ryan, JJ later tells her that she is unaware that Collin is also crushing on her and is more interested in her than she is.
Nancy sent plans to detonate a bomb beneath Italy's financial district, which Bobbi discovers. JJ then reports the bomb threat to Italian Intelligence. Sadly, all they discover is a phony bomb. The Vatican, where Sophie's choir is performing, is Nancy's true target, as JJ and Sophie discover. Nancy, in the meantime, locates one of the bombs and proceeds to a room beneath the Vatican, where she sets a timer and notifies the G7 nations of the global threat. Nancy, Crane, and David are located by Bobbi and JJ. Crane escapes with the kill switch from the bomb, Nancy makes plans to leave the country, and JJ eliminates Nancy's thugs. Connelly stops David when he tries to follow Nancy. Nancy has to flee while David tries to persuade Connelly that he has not gone rogue.
Sophie and Collin meet Ryan outside the Vatican, where the choirs are playing. When Sophie sees two suspicious guards-who also happen to be Carlos and Todd from the last film-she decides to speak with her choir teacher. Carlos discloses that Crane hired them. They attack Sophie when she tries to get information from them. Sophie gains the upper hand when Collin and Ryan briefly divert Carlos and Todd, but Ryan flees. Sophie eliminates them and then proceeds to assist JJ, who is pursuing Crane through the streets. Together, Sophie and JJ defeat Crane, but the kill switch tumbles into a river. With two seconds remaining, they both swim together to locate the kill switch and detonate the bomb. Sophie requests to accompany them as an ambulance gets ready to transport JJ to the hospital, claiming that JJ is her father.
Collin, meanwhile, plans to prevent Nancy from leaving the country after he spots her strolling through the city. Nancy immediately threatens to kill him. Speaking Italian fluently, Collin creates a scene by accusing Nancy of being his violent mother. This stops Nancy from leaving, enabling David and Connelly to track her down and take her into custody.
Later, when Sophie and Collin are together on an Italian rooftop, Sophie confides in him that she has come to the realization that Ryan is not the right person for her. Collin accepts her invitation to the homecoming dance. JJ and David are shown elsewhere, watching the two of them via satellite as they share their first kiss. David tells JJ that he and Bobbi are now formally dating.
David, Kate, and JJ welcome their children home from their field trip back in Langley. But it turns out that there are parakeets in a few of David's car's suitcases, and they perch on David. Unsure of what to do, JJ and David choose to flee as the parakeets pursue them.
