In the vibrant state of Arizona, Dignan — brilliantly portrayed by Luke Wilson — orchestrates an elaborate scheme to "rescue" his friend Anthony, who has been residing in a voluntary psychiatric unit due to what he describes as exhaustion. Dignan's ambitious aspirations involve a meticulously crafted 75-year plan that he excitedly shares with Anthony, which outlines a series of heists culminating in a meet-up with the enigmatic Mr. Henry, a local landscaper and part-time criminal known to Dignan.
As part of their practice for the big heist, the duo breaks into Anthony's family's home, where they pilfer specific items from a pre-arranged list. However, calamity strikes when Dignan admits to swiping a pair of earrings, which he had not included on their list. This theft deeply frustrates Anthony, given that he had bought those earrings as a gift for his mother. In a moment of reconciliation, Anthony seeks out his little sister, asking her to return the earrings in question.
In a twist of fate, Dignan enlists Bob Mapplethorpe — played by Owen Wilson — as their getaway driver, simply because he possesses a car. The trio embarks on a new adventure, procuring a gun and going over their next heist plan, which targets a local bookstore, amidst some friendly squabbles as Dignan struggles to articulate his complex strategies.
After successfully acquiring a modest amount from the bookstore, they go "on the lam" and retreat to a motel, where Anthony meets Inez, one of the maids. Their romance blossoms against the backdrop of a language barrier, with Inez speaking little English while Anthony knows no Spanish.
However, Bob faces his own demons when he discovers that his marijuana crop has been found by the police, leading him to leave the group abruptly to assist his arrested brother. Before departing, Anthony entrusts Dignan with an envelope to deliver to Inez, not realizing it contains most of their hard-earned money. As Dignan hands over the envelope, Inez hugs him goodbye, blissfully unaware of its contents. In a stroke of miscommunication, Inez's friend later rushes to inform Dignan that Inez loves Anthony, a message he fails to convey.
Moving forward, Dignan stumbles upon a beat-up yet operable Alfa Romeo Spider, and together he and Anthony strive to put their expansive plan into action. Following a series of unfortunate events, including the breakdown of their vehicle and the realization that Dignan lost their money through a misplaced envelope, tension mounts between the friends, ultimately forcing them to part ways.
In a reflective letter to his sister, Anthony indicates he and Bob have returned home to a routine life. Dignan, now part of Mr. Henry's gang, seeks reconciliation with Anthony, who agrees to join a heist under the condition that Bob is included.
Their venture introduces them to the colorful Mr. Henry, who serves as a mentor figure, offering guidance and bolstering their confidence. In between preparation for a significant heist at a cold storage facility, fostering deeper connections with Inez, and navigating friendships, the stakes rise dramatically. Unfortunately, their carefully laid plans quickly unravel as complications emerge during the heist that includes misfires and unexpected medical emergencies.
As the situation escalates, Dignan finds himself in a precarious position, locked out of the escape van and subject to police brutality. In a poignant moment, Anthony and Bob arrive at the prison, relaying that Mr. Henry has been robbing Bob's house all along.
As they bid farewell, Dignan attempts to maintain his bravado, outlining yet another escape plan, before delivering a final quip, “Isn't it funny that you used to be in the nuthouse and now I'm in jail?” as he strolls back into the prison, leaving behind a whirlwind of misadventures and shattered dreams.
