Blood is played from a first-person perspective across interconnected levels filled with combat arenas, locked doors, switches, traps, secrets, and hidden areas. The main objective is to reach each level's exit while collecting keys, ammunition, armor, health, and weapons.

The original DOS campaign is divided into four episodes, each with its own locations and boss encounters. Caleb can carry multiple weapons and use alternate attacks, while explosives and environmental hazards reward careful positioning. Enemies vary from cultists and undead creatures to large supernatural monsters, and multiplayer modes support competitive deathmatch and team-based play.

Search every room for hidden switches, destructible surfaces, secret areas, and alternate routes. Ammunition and health can become scarce, so reserve powerful weapons and explosives for dangerous enemies or crowded encounters.

Use the environment to your advantage. Explosives can damage groups, flares can ignite vulnerable targets, and many enemies are easier to defeat from a doorway or elevated position. Save before major fights and learn enemy attack patterns rather than rushing into open spaces.