Due to a political conspiracy, an innocent man is sent to death row and his only hope is his brother, who makes it his mission to deliberately get himself sent to the same prison in order to break the both of them out, from the inside out.
Now locked up in a Panamanian prison known as Sona, Michael, T-Bag, Bellick, and Mahone try to find a way out. Much to their devastation, they soon find out that the prison has been abandoned by the authorities because of the immense threat from the vile inmates. Michael seeks for an inmate named Whistler in the prison sewers. As Lincoln is puzzled by Sara's sudden disappearance, he learns that LJ has gotten into some trouble. He also tries to recover the 5 million dollars.
Michael and Mahone try to lure Whistler out of his hiding place. T-Bag gains some upward momentum in the prison hierarchy as the water supply is running low. Lincoln meets familiar and not so familiar faces on his quest to free Michael.
Whistler tells the truth to Michael. Michael tries to get in touch with Sara but the only phone is in Lechero's quarters, so he has to rely on T-Bag's help. Mahone battles his addiction. Bellick steps on some toes.
After taking delivery of a package from The Company, Lincoln realizes that they are deadly serious. Michael's new break out plan relies on electricity. Haywire is back from the dead, haunting disoriented Mahone. Bellick and T-Bag get special attention from Lechero.
A new inmate named Tyge is brought to Sona. After he seemingly recognizes Whistler, Michael's doubts arise. T-Bag enters a new area of commerce.Lincoln goes to the seaside with Sofia. Sucre takes over the side-business of his predecessor.
Michael threatens to cancel the escape plan unless he sees a proof that Sarah is still alive. Whistler is accused of murdering an inmate and it is up to Michael to prove his innocence and save his life. Lincoln and Sofia help in monitoring the morning guards. Mahone may have another way to get out of Sona.
Everything goes wrong for Michael as he tries to create a diversion.
Lincoln tries to outsmart Susan who has his son. Sucre offers his assistance to Lincoln.
Susan jeopardizes Michael's life as she puts her own escape plan into motion. Whistler's past catches up to his girlfriend.The Company goes after Lincoln and Sucre. Justice prevails for Mahone. And Lechero sheds light into an empty tunnel.
The Panamanian Army arranges Michael to get a taste of solitary. T-Bag reserves a spot in the escape. Bellick's life turns into an uphill battle. Susan traps Sucre.
Lechero's demotion devastates Michael's breakout plan as Sammy takes reigns at Sona. T-Bag forces Bellick to fight in a fight where the odds are stacked heavily against him. Lincoln and Sucre have some surprise fireworks set for Susan.
Michael and Lincoln are left with no choice but to hand Whistler over in exchange to save LJ and Sofia. A familiar face enters Sona while another inmate leaves.
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