Perhaps a plot could revolve around Zim as a girl forming different relationships. For example, she might develop a unique friendship with Dib that is different from the typical male - Zim and Dib dynamic. Or she could have a female - centered friendship that helps her navigate the human world in a new way.
A possible plot could be that Zim, as a girl, discovers new aspects of her identity. She might start to question the Irken way of life more deeply. She could also be more in tune with emotions like empathy, which could lead her on a different path in her attempts to conquer Earth. Maybe she realizes that there are better ways to interact with the humans than just through invasion and destruction.