Studies suggest that serious games are useful tools for disaster preparedness training, but few have examined if instructional factors differentially affect the learning outcomes. This study investigated the effects of players' gaming frequency, prior knowledge, and in-game guidance received on their declarative and procedural knowledge in a disaster preparedness serious game. Findings showed that gaming frequency was not a significant predictor for learning outcomes. By contrast, players' prior knowledge, the types of in-game guidance received, and the interaction between the two were all significant predictors for the acquisition of declarative knowledge and development of procedural knowledge. The interaction term revealed a moderator effect, indicating that the relationship between a player's prior knowledge and learning outcomes was affected by the type of in-game (full or partial) guidance received.