Businesses have closed and streets have been shut around the Vatican residence in the city, while police have been making door-to-door enquiries nearby.
The first papal trip to the country in 17 years comes after suicide bombings at Coptic churches in Tanta and Alexandra on Palm Sunday left 45 people dead.
Islamic State claimed responsibility for the attacks, as it previously did for a suicide blast on a cathedral in Cairo on 11th December which claimed 25 lives.
Nevertheless, Pope Francis shunned a bullet-proof vehicle, insisted choosing to travel through the city's street in a closed but unarmoured car.
The trip is aimed at being a sign of solidarity with Egypt's beleaguered Christian minority - which has been specifically targeted by Islamist extremists - and a bid to strengthen ties with the Muslim community.
After a meeting with President Sisi, the Pope will met the Coptic pope Tawadros II and Egypt's most senior Iman, Sheikh Ahmed al-Tayeb.