The Street Sharks have suddenly become human again due to a formula made by Dr. Piranoid as part of a plot to keep the Street Sharks human permanently.

Dr. Paradigm is visited by his future counterpart in his Time-Slammer where they work on a plan to develop a mechanism to alter the world's genetic code by New Year's Eve. The Street Sharks are tipped off about the disturbance in the time-space continuum by Dr. Bolton and work with Mantaman and El Swordo to thwart the two Dr. Paradigms and the future Dr. Paradigm's Mechosharks.

Malcolm Medusa III and Clammando are back and have been hunting Florida panthers in the Everglades as part of a plot to develop a chemical waste incinerator there. After Moby Lick has been caught by Malcolm when trying to rescue them, the President enlists the Street Sharks to investigate where the trace the Florida panthers and Moby Lick to a nearby island where Malcolm has used a petrifying laser to petrify Moby Lick, the Florida panthers, and other wildlife in the Everglades. Now Malcolm plans to have the Street Sharks provide a hunting challenge for him.

At the time when the World Leaders have come to an agreement not to use biological weapons, the Street Sharks and the Dino Vengers are enlisted to guard a top secret facility that the biological weapons are going to be safely destroyed. In order for the Raptors to prevent the biological weapons from being destroyed, Dr. Paradigm (who is now Dr. Iguanoid) puts the finishing touches on his mind-control chip which they plan to use on Bad Rap's alien creation after freeing it. This leads up to Dr. Iguanoid releasing the other alien in the facility as part of his plot to rule Earth.

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.

While the Street Sharks are going out for burgers, Dr. Paradigm transforms a squid he has acquired into Killamari who becomes the latest member of the Seaviates. The Sharks have to stop them from breaking into the Bolton home and stealing important genetic research data that their father left behind.

Dr. Piranoid has Killamari and Tentakill capture Mantaman's younger brother Ryan so that he can get Mantaman to hijack two jets with one of them carrying the Latonian president and the other one carrying the Coachnian president where both of them are to be meeting with President Horne the next day. While Mantaman does the hijacking, Bends and the Street Sharks work on playing along while finding out where Dr. Piranoid is keeping Ryan. During that time, Dr. Piranoid has created the Genesis Satellite to end the world's woes by detonating it so that the world can be turned into mutated creatures.

President Horne contacts the Street Sharks informing them that a UFO has been sighted in the Solar System. Upon investigating, the Street Sharks meet the Dino Vengers T-Bone, Stegz, Bullzeye, and Spike. The Street Sharks learn from them that they are after Bad Rap and the Raptors. The Street Sharks and the Dino Vengers join forces when the Raptors steal different weapons from different countries in order to make the other countries think they are being attacked by the other.

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.

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.

Lena's brother Malik is among those who have been taking strength-enhancing pills. Ripster goes undercover to trace the source of the pills and discovers that a drug dealer named Jackal has been distributing the pills in order to get some recruits to help rob a bank.

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.

Maximilian Greco is back and has established a casino called the Golden Greco while making its surrounding areas as part of Fission City's casino district. Dr. Paradigm sends Repteel and Shrimp Louie to raid the Golden Greco and steal all the money there. Yet Repteel and Shrimp Louie continue to rob other casinos causing Dr. Paradigm to send Killamari after them up to the point where the Seaviants are enlisted by Maximilian Greco to take over the casino district.

A space capsule that landed on Earth 65,000,000 years ago has been unearthed by archaeologists. While Dr. Paradigm has taken interest in the space capsule, an incident involving the capsule's prisoner Bad Rap causes Mantaman to fall under his control (the alien whose DNA was used to create Mantaman was one of Bad Rap's many creations) as they plot to control the largest radio telescope in order to contact Bad Rap's fellow Raptors. Now the Street Sharks must work to free Mantaman before Bad Rap's transmission to his fellow Raptors gets through.

While fighting the Raptors, the Street Sharks and the Dino Vengers hear from President Horne that the military is testing their stealth Super Shadow chopper. As the Street Sharks and the Dino Vengers work to protect the Super Shadow from the Raptors, Dr. Paradigm takes interest in the Raptors as he leads Shrimp Louie and Tentakill into finding them where he will steal the Super Shadow for them in exchange for Velociraptor DNA. After Dr. Paradigm obtains the Super Shadow, the Raptors trick Dr. Paradigm by giving him iguana DNA. The Street Sharks and the Dino Vengers must work to reclaim the Super Shadow from the Raptors.

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

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.

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.

While investigating the killer whale attacks, the Street Sharks and Moby Lick trace the attacks to Malcolm Medusa III's marine animal sanctuary called Medusa Cove which is being covered up by holograms to hide the pollution and trapped whales. They discover that businessman Malcolm Medusa III and Clammando have been using holograms to keep the town from knowing what is really happening.

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.

Fission City has suffered a blackout as Dr. Paradigm unveils the Wolverinepedes (a wolverine/centipede hybrid) which will be a solution to Fission City's toxic waste problems. The Street Sharks are contacted by Paxel of the G.E.C.O.s (short for Genetic Engineered Cave Organism) on behalf of Robert Bolton where they learn that toxic waste is leaking into their underground home beneath the garbage dump. The Street Sharks discover that the Wolverinepedes are a cover for Dr. Piranoid's illegal toxic waste-dumping property where the Wolverinepedes have been getting bigger from the consumption of toxic waste.

At the time when El Swordo is entertaining the USS Liberty, a four-headed sea monster (where some navy officers have compared it to Scylla) has been attacking ships and submarines at sea. To prevent an international incident, President Horne enlists the Street Sharks to look into this. The Street Sharks work with El Swordo in order to keep the four-headed sea monster from attacking ships.

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 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.