After reminiscing about high school, the guys conclude that it would be a public service if they allowed teens to drink in the bar, thus providing a safe and controlled environment for teens to party. Feeling that she missed out on a lot as a teenager due to having to wear a brace for her scoliosis, Dee begins dating a high school jock.
After discovering that he might have cancer, Mac and Dennis attempt to find a woman who will sleep with Charlie. In the midst of their search, Mac falls in love with a transsexual he meets at the bar named Carmen. Overwhelmed by the extra workload that she had to take on since Charlie has taken a leave of absence, Dee tries to get Dennis to hire a recently out of work actress friend to help out.
Dennis and Mac make a decision to take away all rules concerning moral and behavioral etiquette at Paddy's after an argument about the Constitution. Frank uses the decision and it's following consequences to his own gain. Meanwhile, Charlie tries to convey his love for America by protesting while Dee attempts to reaffirm her goal of being an actress.
After Mac arrives to the bar with scratches on his neck and exhibiting strange behavior, Frank comes to the conclusion that he is the serial killer terrorizing young women in Philadelphia. Frank sets out with his trusty chainsaw and a doubtful Charlie to find evidence to implicate Mac in the murders. In search of another suspect, Dennis and Dee do a little role-playing in order to help themselves better understand who they might be dealing with.
Charlie and Dee have been stealing Frank's delicious meats, so Frank leaves out human meat to get back at them. Driven by their cannibalistic needs, Charlie and Dee go in search of human flesh. Mac and Dennis harass Frank for hunting defenseless animals and think it would be much more badass to hunt something that could fight back ... like a human.
Charlie, Mac, and Dennis formulate a plan to take advantage of the rising gas prices. By purchasing excess amounts now, they can sell it in the future and profit. As usual, things don't go as planned. Dee is also out to make money when she learns that Bruce is going to give the family fortune to a Muslim cultural center. She and Frank try to stop him and get the cash for themselves.
Due to the gang's latest "business expenses," Paddy's is in dire need of money. Frank buys a billboard to advertise the bar, but Dee decides to create a viral video to post on YouTube for promotion. Charlie quickly joins her, leaving Frank and Mac to hold a contest for some hot models to feature on the billboard. Naturally, Dennis joins the competition to prove his worth.
Charlie finds out that the waitress has been seeing someone. He calls on Mac, his so-called best friend, to find out more information about the guy and to beat him up. However, it turns out that Mac is the guy the waitress has supposedly been seeing. Dennis, heartbroken that he's not Charlie's best friend, tries to win him over.
After being banned for 10 years from a local drinking competition appropriately named "Flipadelphia," the gang tries to reignite their old rivalry with another local bar. Finding that they are in need of some serious practice, the guys head to Dennis' old fraternity house at the University of Pennsylvania to get their game up to speed while Dee hones her skills on her own. Frank wears skinny pants.
Every member of The Gang has something to celebrate at Guigino's, Philly's finest eatery, but when Mac and Dennis' private dinner is interrupted by an unexpected sighting of Frank and Charlie, the in-fighting begins. Dee also turns up at a table for one, and over the course of the night, the "one-ups-manship" soars to new heights.
The gang takes a trip to a local water park, ripe with personal agendas and ulterior motives. Dennis feeds off his mantra of "the park provides" and takes on a protégé. Frank and Charlie are determined to ride every ride by any means necessary and Mac and Dee get stuck in a tube slide for most of the day.
Charlie thinks Mac's mom is holding his mom hostage, so the gang installs spy cameras in their house to monitor what's going on. What they end up discovering is the moms are quite entertaining once Dennis makes some quick edits and adds a laugh track to the surveillance footage. Dee wants in on the new hit show, and Frank becomes obsessed with banging Charlie's mom now that he's seen her on TV.
The Gang’s in Dublin! Dennis longs for a charming, authentic European experience, but ends up helping Frank with some of his business’s “dirty work.” Mac and Charlie learn about their Irish heritage. Dee rushes to the set of an Irish soap opera, where she will play the role of “Obnoxious American MILF.”
Guided by a young priest, Mac spends a day at the seminary to truly understand what it takes to become a priest. Dennis and Frank plan an elaborate trap at the castle to humiliate Charlie’s pen pal. Dee prepares for a date with an Irish doctor, only to find herself sinking in a bog. Having learned of his pen pal’s true identity, Charlie bonds with him and makes a choice that will forever change the Gang.