A disproportionate burden of infant and under-five childhood mortality occurs during the neonatal period, usually within a few days of birth and against a backdrop of socio-economic deprivation in developing countries. To guide programmes aimed at averting these 4 million annual deaths, recent reviews have evaluated the efficacy and cost-effectiveness of individual interventions during the antenatal, intrapartum and postnatal periods in reducing neonatal mortality, and packages of interventions have been proposed for wide-scale implementation. However, no systematic review of the empirical data on packages of interventions, including consideration of community-based intervention packages, has yet been performed. To address this gap, we reviewed peer-reviewed journals and grey literature to evaluate the content, impact, efficacy (implementation under ideal circumstances), effectiveness (implementation within health systems), type of provider, and cost of packages of interventions reporting neonatal health outcomes. Studies employing more than one biologically plausible neonatal health intervention (i.e. package) and reporting neonatal morbidity or mortality outcomes were included. Studies were ordered by study design and mortality stratum, and their component interventions classified by time period of delivery and service delivery mode. We found 41 studies that implemented packages of interventions and reported neonatal health outcomes, including 19 randomized controlled trials. True effectiveness trials conducted at scale in health systems were completely lacking. No study targeted women prior to conception, antenatal interventions were largely micronutrient supplementation studies, and intrapartum interventions were limited principally to clean delivery. Few studies approximated complete packages recommended in The Lancet's Neonatal Survival Series. Interventions appeared largely bundled out of convenience or funding requirements, rather than based on anticipated synergistic effects, like service delivery mode or cost-effectiveness. Only two studies reported cost-effectiveness data. The evidence base for the impact of neonatal health intervention packages is a weak foundation for guiding effective implementation of public health programmes addressing neonatal health. Significant investment in effectiveness trials carefully tailored to local health needs and conducted at scale in developing countries is required.