When Marcella Leones relocates her family of aswang vampires from the Philippines to Portland, Oregon, she raises her grandchildren under strict rules so humans will not expose them. Her only wish is to give them a peaceful life, far away from the hunters and the Filipino government that attempted to exterminate them.

Before she dies, she passes on the power to her eldest grandchild, Percival. He vows to uphold the rules set forth by Leones, allowing his family to roam freely without notice. After all, they are aswangs.

However, when the aswang covenant is broken, the murder rate in Portland rises drastically. Who is behind the murders? And who is behind the broken covenant? Along with sensie Penelope Jane, Percival must find the truth.

It's then they discover that there are other breeds of aswangs—werebeasts, witches, ghouls, and viscera—who have been residing in Portland for years.

Based on Filipino folklore (aswang), "Vampires of Portlandia" is a fantastical tale of different monsters coexisting in the weirdest city in America.