BACKGROUND: The COVID-19 pandemic has had an unprecedented impact in the global research production and has also increased research waste. Living evidence syntheses (LESs) seek to regularly update a body of evidence addressing a specific question. During the COVID-19 pandemic, the production and dissemination of LESs emerged as a cornerstone of the evidence infrastructure. This critical interpretive synthesis answers the questions: What constitutes an LES to support decision-making?; when should one be produced, updated, and discontinued?; and how should one be disseminated? METHODS: Searches included the Cochrane Library, EMBASE (Ovid), Health Systems Evidence, MEDLINE (Ovid), PubMed, and Web of Science up to 23 April 2024 and included articles that provide any insights on addressing the compass questions on LESs. Articles were selected and appraised, and their insights extracted. An interpretive and iterative coding process was used to identify relevant thematic categories and create a conceptual framework. RESULTS: Among the 16,630 non-duplicate records identified, 208 publications proved eligible. Most were non-empirical articles, followed by actual LESs. Approximately one in three articles were published in response to the COVID-19 pandemic. The conceptual framework addresses six thematic categories: (1) what is an LES; (2) what methodological approaches facilitate LESs production; (3) when to produce an LES; (4) when to update an LES; (5) how to make available the findings of an LES; and (6) when to discontinue LES updates. CONCLUSION: LESs can play a critical role in reducing research waste and ensuring alignment with advisory and decision-making processes. This critical interpretive synthesis provides relevant insights on how to better organize the global evidence architecture to support their production. TRIAL REGISTRATION: PROSPERO registration: CRD42021241875.