Stan finds Deputy Director Bullock, his supervisor, starting a relationship with Hayley. However, he can't risk saying or doing anything about it because he's up for a promotion at the CIA. Meanwhile, Steve finds Dick Cheney's BlackBerry and uses the contact numbers to play pranks on political figures from around the world.
When Steve brings home a permission slip to take sex ed at school, Stan flips out and demands to teach it himself. However, after Stan unrealistically explains the birds and the bees to Steve, he gets into an accident that causes him to take matters into his own hands. Meanwhile, Roger becomes a bartender in hopes of making something of himself.
When the CIA organizes a father-son baseball game, Stan is determined to show his co-workers that his son is masculine and athletic. Unfortunately, Steve is a geek, so Stan decides to lie and ditches him. But after getting a taste of his own treatment at work, Stan turns to Steve and his sci-fi knowledge to help capture a cyber-terrorist. Meanwhile, Roger goes incognito in a desperate attempt to interact with humans.
When Stan's father passes away, Stan reveals his real father is actually Jack Smith, a super suave spy. Jack convinces Stan to quit the CIA and work with him at the Scarlet Alliance, an ultra-secret spy group. Francine is upset with Stan, who is busy training with Jack for a mission involving uranium, artwork and terrorists. But when the FBI shows up at the Smiths' house looking for an international jewel thief, Francine suspects Jack is the fake.
Stan has to throw a party for his boss and assumes his wife Francine will do all the work, but she refuses. With Stan as party planner, the event turns into a disaster. As a result, Stan's boss relocates Stan and his family to Saudi Arabia, where they quickly get a taste of life on foreign ground. As American and Arabian social norms clash, gender wars heat up.
As the Smiths continue to live in Saudi Arabia, Stan is fully enjoying the male-dominated society, while the rest of the family struggles with the different social norms. Meanwhile, Francine's musical expos on gender roles gets her into trouble, and a brush with death leads the Smiths to return to the United States.
Francine insists that Stan and Hayley spend an entire day together, after their arguments drive her crazy, so they can work out their differences about gun control. However, her plan backfires when he takes Hayley to the "National Gun Association Land", where their conflicting opinions about gun control drive them even further apart. Back home, Roger schemes to get revenge on Steve for eating one of his cookies by convincing him that he's adopted.
Steve becomes a famous author, and the entire family gets caught up in his celebrity, including Stan, who becomes an unbearable "stage parent". After Steve hooks up with an agent, he abandons his family to lead a "Cribs" lifestyle.
As Stan continues to dominate the household, Francine finds herself idolizing a group of women who seem to have it all. She tries to impress them and even lies in order to gain acceptance into their group, until she realizes they aren't as perfect as they seem. Meanwhile, loyalties are tested when Stan gets a new best friend.
After Stan and Roger have a rough day, they get into a fight that leads to a "Freaky Friday"-type switcheroo where they get a taste of life in each other's shoes. But after the excitement of a new life stales, they face each other's problems as Roger is under pressure at work and Stan yearns to be needed. The swap gets out of hand as the family starts to crumble.
After receiving a hefty bonus from work, Stan buys extravagant gadgets while Francine pleads for her dream kiosk. Upset about his lack of support, Francine opens a muffin shop without his approval and gives Stan a taste of life without a housewife. In a desperate move, Stan puts Klaus' brain back into a human body - only to discover it was a huge mistake as Klaus tries to win over Francine. Meanwhile, Steve is convinced he's a teen wolf after watching a horror film.
Because of a past incident at his own prom, where he was lured into a dance with the homecoming queen only to have a pile of pigs dropped on him, Stan wants revenge by showing off that he married a homecoming queen, Francine. A proud Stan accompanies Francine to her reunion, but when they find out that two ballots were lost and that Francine didn't actually win the crown, Stan is devastated. Meanwhile, a dejected Steve is "saved" by a pizza delivery man with a Messianic message.
When Stan goes to Atlantic City for a bachelor party and is shunned by his so-called best friend, Roger steps in and becomes Stan's new sidekick. Their friendship goes to a whole new level, but when they return home and face Francine, Stan realizes that what happens in Atlantic City doesn't necessarily stay there. Meanwhile, Hayley and Steve team up to break up a good-looking couple.
Stan wants Steve to be popular and goes to desperate measures giving him steroids to make him bigger, better, and part of the in-crowd at school. But when the steroids have an unexpected side effect, Steve gets a lot more attention than anyone expected. Meanwhile, after Hayley makes a movie about Francine's life as a housewife, Francine is determined to start a new career as a doctor.
After Steve shows a lack of interest in Stan's job, Stan replaces him with Barry, Steve's malicious friend. Barry frames Steve to eliminate him from the household, but when Steve discovers Barry's weakness, he relies on his CIA skills to save the family. Meanwhile, Roger takes an impressive keg-stand and uses it to become a fraternity brother.
When Francine's birthday brings back haunting memories of a celebrity film moment stolen by George Clooney, Francine's new dream is to destroy the star. But when she tries to win Clooney's heart with the intention of breaking it, Stan actually falls for him and sabotages the plan. Meanwhile, back at home, Roger builds a vineyard and starts up a private sweat shop of foster children.