ABSTRACT The Southern and Central Africa International Center of Excellence for Malaria Research (ICEMR), consisting of the Tropical Diseases Research Centre and Macha Research Trust in Zambia and the Johns Hopkins Malaria Research Institute in the United States, has conducted innovative, applied research to understand the epidemiology of malaria across diverse transmission settings. However, progress towards malaria control and elimination has stalled across many countries in sub-Saharan Africa despite continued and intensified investment, including in Zambia. Novel approaches are needed to better understand epidemiological, entomological, and transmission patterns to strengthen malaria surveillance systems and guide interventions and strategies. Longstanding studies like the ICEMRs provide a unique opportunity to address outstanding scientific questions, explore novel data streams, and integrate research with programmatic efforts to translate scientific knowledge into practice. In this third funding cycle of the ICEMRs, we will leverage the deep understanding we have gained over the past 13 years to explore innovative data streams, metrics, analytics, and surveillance tools to fill knowledge gaps, improve strategic decision-making, and better equip the Zambian National Malaria Elimination Programme and local research institutions to achieve the country’s malaria elimination goals across high, medium, and low transmission settings beyond the duration of this ICEMR program. The theme of this ICEMR renewal application is to harness innovation to transform malaria surveillance into key interventions, derived from the World Health Organization’s Global Technical Strategy for Malaria 2016–2030. These innovative approaches will include the use of crowd- sourced data, volatilomics, machine learning forecasting models, data visualization tools at small spatial scales for local use, and periodic serological surveillance using residual blood specimens. By harnessing innovation and exploring novel data streams, malaria metrics, analytical methods, surveillance tools, and their applications to fill existing knowledge gaps and inform strategies, we hope to transform malaria surveillance into key interventions in collaboration with the Zambian National Malaria Elimination Programme, the President’s Malaria Initiative, and other partners to achieve national and regional malaria control and elimination goals.