Charles Wallace understands that Meg is torn in understanding who she is. She is not like her younger brothers, the twins, who fit in comfortably at school, or like the other kids in school. She is too intelligent and too easily frustrated by the boring rote memorization at school to easily fit in. Yet she is not as different from the norm as Charles Wallace, who is so different that he just accepts his differences and does not even try to fit in with the norm. Charles Wallace just accepts the sense of purpose that draws him to Mrs. Who. Meg can't comprehend this anymore than she can comprehend the ways of the other kids at school. She does not fit in in either place. Thus she is not "one thing or another."
When Charles tells Calvin, "Meg has it tough....." he's talking about his perception of Meg's feelings of not fitting in. Meg already knows that she doesn't fit in with the "popular" or "sports" crowd, but she also feels that she doesn't fit in with any other crowd. She feels like an outsider both at school and with her family. Charles and Meg have a bond, and Charles can feel Meg's confusion and frustration at not fitting in at school, and also not feeling as though she fits in with her family as well. Meg is not easy going and well liked as her younger twin brothers are, nor is she as uncaring about fitting in with others as Charles is. He knows that Meg is not comfortable in her own skin.