Background There is an unmet need for review methods to support priority-setting, policy-making and strategic planning when a wide variety of interventions from differing disciplines may have the potential to impact a health outcome of interest. This article describes a Modular Literature Review, a novel systematic search and review method that employs systematic search strategies together with a hierarchy-based appraisal and synthesis of the resulting evidence. Methods We designed the Modular Review to examine the effects of 43 interventions on a health problem of global significance. Using the PICOS (Population, Intervention, Comparison, Outcome, Study design) framework, we developed a single four-module search template in which population, comparison and outcome modules were the same for each search and the intervention module was different for each of the 43 interventions. A series of literature searches were performed in five databases, followed by screening, extraction and analysis of data. “ES documents”, source documents for effect size (ES) estimates, were systematically identified based on a hierarchy of evidence. The evidence was categorised according to the likely effect on the outcome and presented in a standardised format with quantitative effect estimates, meta-analyses and narrative reporting. We compared the Modular Review to other review methods in health research for its strengths and limitations. Results The Modular Review method was used to review the impact of 46 antenatal interventions on four specified birth outcomes within 12 months. A total of 61,279 records were found; 35,244 were screened by title-abstract. Six thousand two hundred seventy-two full articles were reviewed against the inclusion criteria resulting in 365 eligible articles. Conclusions The Modular Review preserves principles that have traditionally been important to systematic reviews but can address multiple research questions simultaneously. The result is an