The emerging field of synthetic biology aims to engineer novel biological entities. The envisioned future bio-based economy builds largely on “cell factories”: organisms that have been metabolically engineered to sustainably produce substances for human ends. In this paper, we argue that synthetic biology’s goal of creating efficient production vessels for industrial applications implies a set of ontological assumptions according to which living organisms are machines. Traditionally, a machine is understood as a technological, isolated and controllable production unit consisting of parts. But modified organisms, or hybrids, require us to think beyond the machine paradigm and its associated dichotomies between artificial and natural, organisms and artefacts. We ask: How may we conceptualise hybrids beyond limiting ontological categories? Our main claim is that the hybrids created by synthetic biology should be considered not as machines but as metabolic systems. We shall show how the philosophical account of metabolism can inform an ontology of hybrids that moves beyond what we call the “machine ontology”, considering that metabolism enables thinking beyond the dominant dichotomies and allows us to understand and design lifeforms in a bio-based economy. Thus, the aim of this paper is twofold: first, to develop the philosophical ontology of hybrids, and second, to move synthetic biology beyond the problematically limiting view of hybrids.