Tyler Ward receives a phone call from his grandfather, desperately asking for help. After quickly arriving at his grandparent house, he finds the place in ruins and the old man unconscious on a rocking chair. Grandfather finally awakes, and starts to reveal a terrible secret about his past encounters with the supernatural.
Vampire Saga: Pandora's Box is a hybrid game, with gameplay mechanics borrowed from the hidden object and adventure genres in two distinct sections. The scene is presented in first person, from the point of view of the protagonist, and the location can be explored by clicking on exit hotspots to move between connected rooms. The hidden object portions are highlighted with purple clouds and sparkles, that when clicked bring up a separate screen showing a zoom view of the scenery. These locations are filled with assorted objects scattered throughout the scene, and the player has to find and click on all the items listed at the bottom of the screen. The hint button is a compass whose needle spins faster or slower when distant or close to one of the required objects.
Some of the objects are stored in the inventory to be used later on the adventure portions. In these sections, the objective is to solve puzzles by dragging and dropping the inventory items from their slots at the bottom to logical places on the location. For example, a key has to be used over a lock to open a container or door. The main character gives contextual hints to the player, displayed as speech balloons over a portrait at the bottom left.