Zack creates a computer, the Zack Attack 20,000, which he believes will capture Carmen. However, when Carmen escapes with one of the treasures Zack had the computer protect, Ivy decides that she doesn't want to put her faith in it. The siblings go their own separate ways on this case, until Ivy is captured by Carmen.
After the detectives get word of that Carmen stole the Spruce Goose and trashed the airport to do so, they are quite puzzled by this un-Carmen-like action. They follow clues to Chile where they meet up with Carmen- only she's being held prisoner by Sara Bellum. Sara imprisons the detectives as well and reveals to them and Carmen her 'grand scheme'.
Carmen begins to steal items that she once saved from other criminals to lure her ex-partner, Suhara, out of retirement. Suhara joins Zack and Ivy to pursue Carmen - much to Zack's dismay. Zack feels Suhara is too old to be of any assistance. He soon learns to respect Suhara and even though they ultimately lose Carmen, Zack learns a valuable lesson that he'll never forget.
When Carmen attempts to steal several items having to do with military strategies, she is foiled several times by 'The Tigress', a thief with a lot of high-tech weaponry of her own. The Tigress lures Carmen to Antarctica, where she reveals herself to be Ivy in disguise. Carmen was ambushed by Acme detectives and taken away, but escapes when she steals Ivy's CO2 boots Zack invented.
Zack and Ivy manage to capture Carmen in Hawaii. However, Zack loses his lucky rabbit's foot and begins to believe he's cursed with bad luck. Meanwhile, Carmen escapes and tries to teach her superstitious henchwoman, Hannah Lulu that there's no such thing as curses or ghosts. Hannah has a panic attack though when Zack and Ivy scare her at a supposedly haunted site. They manage to capture her but Carmen escapes. She leaves behind something Zack was glad to see again - his lucky rabbit's foot.
Somehow, the world's largest diamond, the Star of Africa, was stolen. The police are baffled and it's up to Zack and Ivy to figure this mystery out. They soon discover that one of Carmen's henchmen tried to double-cross her and keep the diamond for himself. With a little trickery of their own, the detectives recover the diamond.
Carmen's reoccurring nightmare sends to her to seek the help of three Native American shamans to interpret it. Meanwhile, Zack, Ivy and a Native American detective named Billy 'Running Bird', track Carmen to Devil's Tower where the meaning of her dream is revealed. Though Carmen is captured, the shamans let her go. They do not want to go back on their promise - they would interpret her dream in exchange for the return of the items she stole from them.
It is reported that Carmen dies in a plane crash. The grief-stricken Chief is unable to help Zack and Ivy solve a series of clues that Carmen left behind to a final caper. The henchman who solves the most of them will be the new leader of V.I.L.E. Zack and Ivy manage to stop all of the thefts. They then travel to the site of Carmen's reported death to pay their last respects. Suddenly, a little bird delivers a message to "look up". When they do, they see Carmen was alive all that time. She had planned to fake her death to see who was worthy enough to take her place - and it turns out Zack and Ivy are the only ones who can!
Zack and Ivy discover Carmen's underground training facility and go undercover as henchmen in training to try and nab Carmen. However, Carmen discovers them and leads them to a chamber that seems to have no way out. There is one way - an escape into time. Carmen created another time machine and uses it to escape. The detectives use a new Chronoskimmer that the Chief gives them and they trace where Carmen is heading - the future.
Carmen arrives in the year 2101 where she stops a heist of a powerful electro-magnet. Meanwhile, Zack and Ivy arrive at the future Acme Detective Agency where the wacky Future Chief doesn't recognize them. They try to prove who they are but run into a few scrapes with the law. Eventually, they meet up with Carmen in Africa. Although the detectives expose that she is a criminal, she escapes with the magnet and Zack and Ivy end up captured instead.
Zack and Ivy escape from the future and follow Carmen to Rome. There, the detectives are captured and are sentenced to fight each other in the Colosseum games. Luckily, they are spared from having to fight each other to the death. They escape, and discover Carmen's plan - she's going to steal the Colosseum! The detectives realize this is part of her plan to become 'the greatest thief of all time' by stealing objects from the past, present, and future.
When Carmen is captured by a judge bent on sentencing her to life in prison, Zack and Ivy are appointed to her defense team. Carmen was accused of recently stealing the Magna Carta, which she did not steal. Zack and Ivy try to gather evidence to prove Carmen did not commit this particular crime. But is she really involved after all?
Maelstrom, a thief who was caught by Carmen during her time as an ACME detective, escapes from prison, swearing revenge on her. At first, it is reported to the detectives that he died during his escape. Zack and Ivy find out that Maelstrom is alive and see the opportunity to catch both Carmen and Maelstrom. However, when the detectives sneak aboard Maelstrom's ship, he captures them.
Zack and Ivy escape Maelstrom's ship and find out that Carmen still believes that Maelstrom died in his try to escape from the prison. Carmen wants to give him a worthy Viking-like funeral in Norway. Zack and Ivy find her beginning to give him such a funeral and are about to tell her that Maelstrom is alive when Maelstrom appears in a ship beside Carmen. He challenges her to come after him or die and then speeds off. Carmen manages to get Zack and Ivy aboard her ship and they make an agreement to join forces to capture Maelstrom.
When Carmen tries to steal some treasures from industrialist Malcolm Avalon she discovers a painting representing her mother. At the same time, Lee Jordan takes the decision to become the new leader of V.I.L.E. Avalon tells Carmen, that the medallion she has with her, representing the same woman as on the painting, was a gift for his daughter, but he says, that Carmen can't be his daughter because she died in a fire and she would never have become a thief. To convince him she turns herself into the police but when Lee abducts Avalon, she breaks out again.