Research on self-determination theory emphasizes the importance of the internalization of motivation as a crucial factor for determining the quality of motivation. Hence, intrinsic motivation is deemed as an important predictor of learning. Research on epistemic beliefs, on the other hand, focuses on the nature of knowledge, and learning with more sophisticated epistemic beliefs associated with more adaptive outcomes. While learning and achievement are multiply determined, a more comprehensive theoretical model that takes into account both motivational quality and epistemic beliefs is needed. Hence, this study aims to examine the role of intrinsic and instrumental motivation alongside epistemic beliefs in predicting students’ achievement in science. Data were drawn from the PISA 2015 survey. We focused on four of the top-performing societies. Two were Eastern societies – Singapore and Hong Kong, and the other two were Western societies: Canada and Finland. We found both common and specific patterns among the four societies. Regarding the common patterns, we found that intrinsic motivation and epistemic beliefs had direct positive effects on science achievement. As for the regionally-specific findings, instrumental motivation positively predicted achievement only in Western societies (i.e., Finland and Canada), but not in Eastern societies (i.e., Singapore and Hong Kong). The interaction effect between motivation and epistemic beliefs also demonstrated different patterns across the four societies. Implications for the role of motivation and epistemic beliefs in optimizing student learning and achievement are discussed.