Nancy Drew: Secrets Can Kill is a graphic adventure played out in detailed interactive 3D environments. In this adventure, Nancy, who is visiting her Aunt Eloise, investigates the chilling murder of a widely disliked student, Jake Rogers. Aunt Eloise, a librarian, lives near the high school where the heinous crime took place, affording Nancy access to various pertinent locales such as the high school, Maxine's Diner, and a pharmacy. At all times, the player controls which environment Nancy is investigating by using a point-and-click interface that allows examination and manipulation of the game's many objects. In each environment, you must navigate 3D rooms and hallways while searching for clues such as notes left on bulletin boards or objects in drawers. An inventory box near the bottom of the screen houses Nancy's found objects until needed.

In addition to finding clues, you must also solve other types of puzzles. Each area of exploration has its own ambient music and sound effects. During the course of the investigation, Nancy must elicit information from several characters. Each is a 2D cartoon with individual facts and motives, a distinct personality, and personal reactions toward the heroine. When speaking with a character, Nancy is given a choice of questions or comments from which to choose, and, based on the responses she receives, investigates accordingly. If Nancy is killed by stumbling into a booby trap, a "Second Chance" option pops up, which if selected, puts her back in the game immediately prior to the fatal error.

This remastered version of the original game in the popular Nancy Drew series includes 3D characters, new puzzles, an enhanced sleuthing kit, single-disc installation, and an entirely new ending.