This article casts light on the intimate relationship between metaphysics and science in Adam Smith’s thought. Understanding this relationship can help in resolving an enduring dispute or misreading concerning the status and role of natural theology and the ‘invisible hand’ doctrine. In Smith’s scientific realism, ontological issues are necessary prerequisites for scientific inquiry, and metaphysical ideas thus play an organizing and regulatory role. Smith also recognized the importance of scientifically informed metaphysics in science’s historical development. In this sense, for Smith, the metaphysico-scientific link (i.e. metaphysically coherent conjecture), was a basic criterion of scientific validation by Inference to the Best Explanation. Furthermore, Smith’s comments implicitly suggest that in scientific progress there is a dialectic between metaphysics and science. These themes are illustrated primarily through his writings on the history of astronomy.