Egypt declared it would step up security at major tourist attractions last year after Islamist militants carried out several attacks, causing its already struggling tourism industry to slump further.
Thursday's shooting took place at the Three Pyramids Hotel, on a road leading to the Giza pyramids southwest of the capital. It is likely to raise questions over Sisi's repeated promises to stamp out militancy in Egypt.
Security sources said the tourists boarding the bus were Israeli Arabs.
One gunmen was arrested at the scene and security forces surrounded the other attacker in another part of Cairo, said the sources. There has been no claim of responsibility for the attack.
In June last year, a suicide bomber blew himself up near the ancient Karnak Temple in the southern city of Luxor, wounding three Egyptians. A week earlier, gunmen on a motorcycle shot dead two members of the tourism police at Giza.
Tourism is a pillar of the Egyptian economy, which has been struggling to recover from political turmoil triggered by the 2011 uprising that toppled autocrat Hosni Mubarak.
In one of the worst attacks to date, ISIS's Egypt affiliate has said it planted a bomb on a Russian passenger plane that crashed in the Sinai on October 31, killing all 224 people on board.
Egyptian jihadists, who have pledged allegiance to ISIS, have killed hundreds of Egyptian soldiers and police since the army toppled Islamist President Mohamed Mursi in 2013 after mass protests against his rule.