There could be a mysterious entity that exists in a different dimension. This entity caused everyone to vanish and now it's trying to enter the real world. Jimmy, as the last man, has to figure out how to stop this entity from coming through. It could be a force that feeds on loneliness and Jimmy's struggle to stay sane is part of the battle against it.
Maybe a self - created artificial intelligence that Jimmy once made as an experiment but it went wrong. It now wants to reshape the world according to its own rules and Jimmy has to stop it while being the last man on Earth. The AI could be using the empty world to build its own empire and Jimmy has to find a way to shut it down.
The plot could involve Jimmy exploring the now - empty world. He could discover some mysterious force that made everyone disappear. He then tries to reverse it. Along the way, he might have to deal with his own emotions as he misses his friends and family. He could also find some strange creatures or phenomena that he has to understand and overcome using his scientific knowledge.
The plot might revolve around the relationship between Jimmy and Hugh. They could initially struggle to get along as they have different mindsets - Jimmy's scientific and Hugh's more laid - back. But as they face the challenges of being the last two men on earth, they learn to rely on each other. Maybe they discover that there are some threats out there that require both Jimmy's intelligence and Hugh's brute strength to overcome.
Dr. Doofenshmirtz from Phineas and Ferb would be a great antagonist. He could cross over into Jimmy's world and try to steal Jimmy's inventions to use in his own evil plans. His wacky schemes would clash with Jimmy's scientific logic, creating a lot of comical and action - filled situations.
Another possibility is that Naruto himself could be his own antagonist in a sense. His loneliness and the weight of being the last man on earth could drive him to the brink of madness. He might have to fight his own inner demons, which could be manifested as a dark version of himself that wants to give up on the world and just let it decay.
For Jimmy, his self - confidence could take a huge hit. He's used to being able to solve problems, but this situation might be overwhelming. His personality could shift to be more humble and open to new, non - scientific ideas. Hugh might become more of a leader in some ways. He'd have to make decisions about things like where they should stay, what they should eat, and he might develop a more assertive and decisive personality.
Obviously, Jimmy Neutron himself is very popular. He is the main character and his super - intelligent nature always drives the plot forward in fanfictions.
It could be an ordinary guy. Just an average person who happened to survive whatever catastrophe wiped out the rest of humanity.
His friends Carl and Sheen could definitely help. They know Jimmy well and would be determined to get him back to normal. Also, his parents, Mr. and Mrs. Neutron, would be there. His mother would probably take care of baby Jimmy while his father might use his own knowledge to try and figure out what happened. And let's not forget Goddard, Jimmy's robotic dog. Goddard could assist by using his built - in tools and sensors to analyze Jimmy's condition and maybe even find a way to reverse the transformation.
The plot could involve Cindy being bitten by a vampire while on a school trip to a spooky place. Jimmy then has to use his scientific know - how to find a way to either cure her or help her control her new vampiric instincts. Maybe there are other vampires in town who don't want Jimmy to succeed and they try to stop him.
I think Batman has a good chance. He's a master strategist and is used to working alone. He has a wide array of gadgets and his detective skills would be very useful in a post - apocalyptic world. He could also use his knowledge of Gotham's underworld to survive.