Burn-in is a technique to enhance reliability by eliminating weak items from a population of items having heterogeneous lifetimes. System burn-in can improve system reliability, but the conditions for system burn-in to be performed after component burn-in remain a little understood mathematical challenge. To derive such conditions, we first introduce a general model of heterogeneous system lifetimes, in which the component burn-in information and assembly problems are related to the prediction of system burn-in. Many existing system burn-in models become special cases and two important results are identified. First, heterogeneous system lifetimes can be understood naturally as a consequence of heterogeneous component lifetimes and heterogeneous assembly quality. Second, system burn-in is effective if assembly quality variation in the components and connections which are arranged in series is greater than a threshold, where the threshold depends on the system structure and component failure rates.