Resorts World Manila was put on lockdown after the incident, which happened shortly after midnight local time (16:00 GMT).
Swat teams were deployed to the scene, and TV footage showed people fleeing the hotel in panic.
The Philippines police chief said they did not believe it was a terror attack.
Ronald dela Rosa said a lone gunman had entered the gaming area at Resorts World and set some tables on fire.
Gunshots were fired, he said, but were not aimed at people in the room.
Mr Dela Rosa told local radio station DZMM that the incident may have been a robbery. He warned that Islamic State militants might falsely claim to be behind it to further their propaganda.
"We cannot say this is an act of terror ... he [the gunman] did not hurt anyone," he said. "If you are a terrorist you will sow terror."
Resorts World Manila features multiple hotels and bars, as well as a casino, shopping centre and cinema.
There are no current reports of people being injured in the incident there, which many witnesses took to be a militant assault attack.
Maricel Navaro, a Resorts World employee, told DZMM he had returned from his break to find people fleeing in panic.
"Guests were screaming. We went to the basement locker room and hid there. People were screaming, guests and employees were in panic.
"When we smelled smoke, we decided to go for the exit in the car park. That's where we got out. Before we exited, we heard two gunshots and there was thick smoke on the ground floor."
Eyewitness Hessa Isabelle filmed the scene from a nearby balcony and described seeing "people screaming and running out of the building".
"People are being evacuated out of the building and there's smoke coming out, and they're saying that it's a terrorist attack," she said.
The US state department tweeted a warning to citizens, stating: "Reports of explosions/gunfire at Resorts World Manila, near the Manila Intl Airport. Avoid area & monitor local news."
President Donald Trump labelled the incident a terror attack, and offered his "thoughts and prayers" to those affected.
"We're closely monitoring the situation ... but it is really very sad as to what's going on in the world with terror," he said.
The incident comes as the Philippines army is fighting militants linked to the so-called Islamic State group for control of the city of Marawi on the southern island of Mindanao.