Her visit will wrap up what has been considered a successful trip, where she has been promoting her Be Best program, focusing on things like cyberbullying and wellbeing.
Mrs Trump's week-long trip to the continent is seen as an attempt to heal some of the divisions.
Reports of her decision to wear a white pith helmet - a symbol of British colonial rule - in Kenya visibly frustrated her.
The U.S. first lady's tour in Cairo is expected to include visits to schools and public hospitals and meetings with mothers and children, as the trip focuses on children's health and well-being.
University of California political science professor Kim Yi Dionne, who started the hashtag, said Ms Trump reinforced colonial attitudes with her clothing choices.
On her first stop, Melania visited children at a healthcare center with the country's First Lady before laying a wreath at at a slave fortress on the coast of Ghana. "That's very important, what I do, what we're doing with USAID, my initiatives, and I wish people would focus on what I do, not what I wear".
It's not the first time her outfits have garnered criticism.
Ms Trump's focus on wildlife stands in contrast to efforts by her husband to lift a ban on some elephant trophy imports, which created a public outcry past year.
Defending her controversial outfits on a recent Africa trip, the 48-year-old posted a video broadcast from Egypt saying: "I want to talk about my trip, and not what I wear". She seemed to ponder the question. The first lady was quickly encircled by the gleeful children and she smiled and danced some more.
Melania Trump concluded her trip to Africa on Saturday by voicing support for her husband's embattled Supreme Court nominee and urging people to pay less attention to what she wears.
Mrs. Trump arrived in Cairo on Saturday after a flight from Kenya. Or at least his Twitter account.
The stylish former model also said she did not always agree with her husband's tweets and gave him her opinion directly, even though he does not always follow her advice.
Her husband can not be trusted to follow through with whatever good influence she might have on him, not to mention his January 11 remark denigrating African countries that provoked a fierce, continent-wide reaction.