The show's fifth season begins with Vince and Turtle on a beach in Mexico, while Eric and Ari try to get Vince an opportunity to get his career back on track back in California. Medellin has gone straight-to-DVD, and made numerous worst-of-the-year lists, with Vince's performance coming under fire from critics as well. Drama is also in Hollywood, continuing production of his show Five Towns while maintaining a long-distance relationship with his French girlfriend Jacqueline. Ari and E remain unsuccessful in convincing Vince to return to the States until Ari gets a sit-down for Vince with producer Carl Ertz about a new movie titled "Danger Beach". When Vince and Turtle return, they all realize that Ertz was not actually interested in Vince but was instead using him to secure Emile Hirsch for the role. Seemingly at a dead end, Vince returns to basics and begins reading scripts Ari claims are already taken. One sticks out to Eric; Named Nine Brave Souls. Meanwhile Drama's nervousness about Jacqueline possibly cheating on him leads to their break-up and he works himself through a guilty frenzy that reaches its peak when he breaks down during a guest appearance on The View. Eric sees potential in Nine Brave Souls and approaches the writers to begin representing them. He gets Ed Norton and Amanda Daniels (Carla Gugino) interested, and they change the name of the movie to Smoke Jumpers. When Ari finally reads the script of Smoke Jumpers he convinces Eric to start a bidding war for the movie with Vince attached. Amanda refuses to participate and passes on it until later reconsidering and making an offer. However, Alan Gray, the man who fired Vince from the sequel to Aquaman, outbids them.
Ari asks for the second lead in Smoke Jumpers for Vince but Alan Gray says no. Vince is offered a role in a live-action "Benji" movie but after considering it he realizes that Smoke Jumpers is still the movie he really wants. Ari, determined to get Vince the role he desires, challenged Alan to a round of golf for the part. Alan brings PGA Tour pro Phil Mickelson along as a coach and beats Ari. Venting his anger, Alan begins to yell at Ari for even bringing up Smoke Jumpers, knowing he hates Vince; but suddenly drops dead of a heart attack. At Alan's funeral, Ari takes the opportunity to ask John Ellis, Alan's boss, about giving the role to Vince. Ellis instead offers him Alan's position as president of the studio, with Amanda Daniels (Carla Gugino) as the number-two choice for the job. Rather than accepting the offer and abandoning his clients, Ari instead gets Dana Gordon the job, therefore locking up Smoke Jumpers for Vince. Meanwhile, Turtle meets Jamie-Lynn Sigler on an airplane and the two hit it off, but their potential relationship is ruined when Turtle tells the guys she gave him a handjob and they tell everyone. It was revealed to be true.
Smoke Jumpers begins filming and Vince becomes increasingly angry when his co-star, Jason Patric, steals several of his lines. He discovers that the director, Verner (Stellan Skarsgård), gave his lines to Patric. Vince talks to Verner about his frustration over how few of lines he's been given, and rather than giving him more, he tells Vince about his bad acting habits. Ari signs his old colleague Andrew Klein (Gary Cole) as a new partner in MGA.
Verner eventually fires Vince from Smoke Jumpers when one scene is shot several times without good results and Vince gets angry. Ari flies in but cannot convince Verner to give Vince another chance, so he seeks Gordon's intervention. She scolds Verner but he storms into a conference room where Ellis is hosting a meeting. Furious, Ellis pulls the plug on the whole movie. Meanwhile, Jamie-Lynn forgives Turtle for opening his mouth and appears to want to start a relationship with him if he keeps quiet, so they spend the day together and consider spending the weekend together. However, their plans are cut short when he receives a call from Vince explaining the situation and they all fly back to Queens for a week.
With Vince's future in acting looking dim, his relationship with Eric is tested when Vince pursues a role in Gus Van Sant's new film. Eric persistently tracks down Gus in an attempt to convince him to meet with Vince, despite Ari's opposition. Gus refuses, saying he has seen all of Vince's work and he is not a fan, but agrees to see the Smoke Jumpers footage. Meanwhile, Jamie-Lynn reveals her relationship with Turtle to the guys. Gus calls back saying he loves the footage and claims that he would love to work with Vince, but not on his current project. Vince gets really upset and fires Eric, believing that Eric had made Vince look desperate. A heartbroken Eric returns to Hollywood to concentrate on another one of his clients, a young and rising comedian named Charlie played by Bow Wow. Vince later apologize after learning that Eric's persistence led to an offer by Martin Scorsese for a lead in his next feature, a re-envisioning of The Great Gatsby set in the Upper West Side of New York City. The episode ends with them all back in Hollywood on their way to celebrate. The final episode also includes a cameo appearance by Michael Phelps.