The story begins shortly after Sam escapes a volcanic eruption on an Indonesian island. Rather than finding rest, her boss at Uncharted magazine—a scientific publication described with humor as "Playboy for scientists"—dispatches her to Africa to chase a groundbreaking story.

Secret Files: Sam Peters adheres to traditional adventure game standards while utilizing an optimized interface.

The majority of challenges are inventory-based, requiring Sam to combine items to solve environmental obstacles. For example, one sequence involves using syrup and a paintbrush to catch fast-moving ants for a biological sample.