The Street Sharks are framed and brought out of hiding by Sharkbot, the robotic machine built by Dr. Paradigm in the last episode. The Street Sharks must once again defend their reputations and take on Sharkbot.

The Street Sharks are sent to a future where Dr. Piranoid controls everything. They meet up with Bends' great-great-grandson General Bendsini and join the rebel forces.

The Street Sharks and Bends travel to the country of Chernosium to help a child named Ilya (who had sent them a fan letter), rescue his father President Andre Knezevic, and overthrow a dictator named Ekerson Nozum.

After extracting alien DNA from a sample found on an asteroid, Dr. Piranoid tries to gene-slam the entire planet with this alien DNA mixed with manta ray DNA. The Street Sharks are sent up to space, per the president's request and help, to not only stop Dr. Piranoid's gene slamming plan, but also defeat the alien monster that was released from the sample. They end up getting help from Dr. Terrence Morton (who ends up becoming Mantaman in order to help fight the alien.)

Dr. Paradigm captures Big Slammu to control his mind and the Street Sharks must break into Dr. Paradigm's hideout to save their brother.

When his hotel had been previously destroyed by the Street Sharks and no family members to live with, Mr. Cunneyworth allows Dr. Paradigm to gene-slam him with the DNA of an electric eel and a moray eel which transforms him into Repteel. While Repteel is ordered by Dr. Paradigm to steal an advanced supercomputer part for his robotic machine, the Street Sharks take a cruise around the city to find the doctor's new Seaviate's location and put a stop to their evil plans.

The Street Sharks discover an underground civilization of mutant crocodiles that happen to know Dr. Bolton after he cured them of their damaged genes. Meanwhile, Dr. Paradigm rebuilds Sharkbot and captures one of the mutant crocodiles.

When Streex has been captured by Dr. Paradigm, the rest of the Street Sharks alongside Moby Lick take to the roads to rescue him.

The Street Sharks go to Washington D.C. to save President David Horne from being "gene washed" by Dr. Piranoid as part of his plot to control President Horne after he had successfully gene-washed Vice-President Russell.

When the Street Sharks and the Dino Vengers stop the Raptors from stealing a submarine, Stegz, Spike, and Bullzeye come down with a virus with the same symptoms as the virus the Dino Vengers once contracted on the planet Zirus 10. The Street Sharks and T-Bone race against time and the Raptors to the Amazon Rainforest to get to a special pharmaceutical fungus that would help cure the sick Dino Vengers before its final symptom takes its toll on them in the next 24 hours.

In order to track the Dino Vengers to their lair, the Raptors cause havoc at an amusement park and ambush the Dino Vengers where they managed to secretly place a tracking device on Stegz so that they can find the Dino Lair. When the Dino Vengers end up defeated and captured as part of Bad Rap's plot to launch them to the stars in a stolen missile, the Street Sharks must rescue the Dino Vengers before the Raptors can launch the missile they are on.

Ripster, Jab, Streex, and Slammu must protect their reputations and change the way they are being viewed in Fission City. They must fight Dr. Piranoid as well as finding their father once and for all.

The Street Sharks are on a runaway from the police along with their friends Bends and Dr. Lena. The Street Sharks must find a new place to live in and be safe from society.

The citizens of Fission City hear an announcement from Dr. Paradigm that he has invented a vaccine against the gene-slamming formula.

Rox is back in town for the Fission City Music Awards and plans to play the evidence that would expose Dr. Paradigm's gene-slamming activities.

Mantaman returns to Earth to help the Street Sharks fight the energy-draining alien (which survived the space station's destruction in "Space Sharks") before it starts draining Earth's electricity.

At the time when Big Slammu prepares for Fission City's comic book convention at a local convention center to meet his favorite comic book writer Jake Langstrom, Bullzeye learns about comic books and follows Big Slammu to the convention center. At the same time, the Raptors head to the Munitions and Armaments section of the Convention Center in order to steal the latest weaponry there.

With the help of a mind-control serum, Dr. Paradigm turns Jets Taylor into a killer whale mutant named Moby Lick to be his latest Seaviate.

Dr. Robert Bolton had invented a gene-slamming device for peaceful uses until his colleague Dr. Luther Paradigm uses it for his evil purposes. When Dr. Bolton tries to intervene, he ends up gene-slammed into an unseen inhuman creature during the struggle and escapes. While in search of their father, John, Clint, Robert, and Coop are mutated into humanoid sharks by the evil Dr. Paradigm. While adapting to their new looks, the four brothers must avoid being seen.

When a musician called Melvin Kresnik accidentally digests contaminated popcorn and water that was tainted with a gene-slamming chemical, he becomes a mako shark later known as Rox and befriends the Street Sharks. Together, they have to save the concert in town and its attendants from being mutated into more sea creatures through the same way that Rox was mutated.

Jab and Streex are sent back in time in two different eras by Dr. Paradigm's time machine called the Time Slammer. Back in the present, Slammu, Ripster, and Bends have to deal with Dr. Piranoid's Seaviates who are now joined by Shrimp Louie. With the help of some Atlanteans, Jab is able to travel in time to save his brother Streex.

Dr. Paradigm creates Tentakill as part of his time-traveling plot to have Killamari go back to the medieval times and kill the Street Shark's ancestor Sir Thomas Bolton. Ripster and Big Slammu hijack Dr. Paradigm's Time Slammer to prevent Sir Thomas Bolton from being killed.

At the time when Jab is going to compete in the Cross-Country Grand Prix, Dr. Paradigm creates the Gene-Slam Bomb and places it in the Turbo Jab vehicle so that it would detonate at the Cross-Country Grand Prix if Jab does not have his car running at 65 MPH. The plot thickens when the International Trade Conference that is signing the Big Trade Agreement is threatened by Dr. Paradigm's Gene-Washing Bomb within an ice sculpture of two dolphins.

The Stromboli Circus is in town where El Swordo and his swordfish Spike are the main attraction. Spike is soon targeted by Dr. Piranoid so that he can mutate and control it with the Chromifier Ray so that he can gain control of a satellite and control every head of state in the universe.

An aged crime boss named Maximilian Greco discovers Ripster and Streex fighting Killamari and Repteel at a nearby zoo as part of Dr. Paradigm's plot to obtain animal specimens for his Genetic Engineering Chamber. Upon tracing Killamari and Repteel back to Dr. Paradigm, Maximilian Greco blackmails him into enhancing him with the strength of a rhinoceros and the longevity of a desert tortoise. Maximilian also has Dr. Paradigm have his chihuahuas Zeus and Apollo enhanced to fight the Street Sharks.