As a character, Sis's weaknesses are few, but they're big ones. The first, and most prevalent, is a severe overestimation of her own abilities. While she is indeed very capable, she is neither invincible nor infallible- but both those things are things she often forgets. Instead, her belief in herself is so thorough, so absolute, that she becomes something of a liability to herself and to those around her in certain situations. She means well when she does it, but it does not often go well for her.

Her biggest emotional weakness, however- though she'll try her best to hide it and fail somewhat spectacularly in the right circumstances- is Dave. She will do literally anything for him, despite how unwise the course of action might be or what it may cost her. A person can only act like they're so detached to someone they've spent a good thirteen years raising, and Sis is no exception, no matter how hard she pretends.

As far as weaknesses in her abilities, while her speed and strength are somewhat absurd for what is a 'normal' person, they are nowhere near as high as some of the stronger characters in her canon. While her speed is more or less unmatched, characters with spatial manipulation abilities can easily outmaneuver her. And while she's also quite strong, she's not nearly as strong as one of the Egberts, or even one of the tipsier Lalondes.