Veterinarians equipped with tranquiliser guns and a police helicopter circling overhead began combing the area around the village of Oldeberkoop where the animal shelter is located.
Police later said they spotted the two tigers around 11:00 am and local residents have been warned about the escape.
"We are going to try to bring the animals back to the shelter safe and sound," police said.
Authorities added it was possible the tigers escaped through an open gate, according to the Dutch news agency ANP.
The goal is to eventually transfer the animals to a sanctuary in South Africa.