This article presents a human factors theoretical framework aimed at understanding learning in games as a meaning-making process. The framework models the gameplay activity as a process intrinsically driven by learning, conceptualizes game-based learning as a meaning-making process central to any type of game, and identifies aspects of a game system key to originate and influence such process. During gameplay, players continuously interpret changing scenarios, decide and plan action in order to pursue desired goals, execute planned actions, and evaluate results. Through this process, the gameplay experience unfolds as a holistic activity that integrates players' thinking, feeling and doing: players define their courses of actions based on the interplay of their perceptions, feelings and thoughts, which are in turn shaped by the outcomes of their actions and other relevant events unfolding in the game space. Through gameplay players explore the game space in order to make sense of the properties and relationships of game entities and events, their patterns of interaction, and the socio-cultural valorization that all this has within the game context. Accordingly, players learn continuously about what happens in the game, how and why, and, by extension, define what is meaningful to them, what they should do, how and why. Understanding the nature of this process and the key game elements that define it is crucial to identify learning potentialities offered by existing games, or design learning affordances for newly created products. We use an example to show how the framework can facilitate both the analysis and design of games from a learning perspective.