SUMMARY Ghana is one of the countries with the greatest Plasmodium falciparum malaria burden, with case trends increasing in recent years. There is a critical gap in research and programmatic efforts to understand malaria epidemiology in urban settings in high-burden countries. The overall research goal of this project is to generate the evidence base to determine strategies to effectively monitor and target interventions appropriate for urban environments in Accra, Ghana, a typical African city in a high-burden country. Through paired clinical incidence data and three household-based cross-sectional surveys in 13 health facility catchment areas, we will: 1) characterize the malaria epidemiology across a transmission season using reported clinical incidence and household-based surveys; 2) Quantify the degree of bias in routine surveillance data due to non-care-seeking malaria infections in an urban setting; 3) Assess the ability of routine malaria surveillance data to identify fine-scale spatial heterogeneity of malaria infections; and 4) determine the degree of infections clustering in households to justify whether targeted strategies are appropriate for the urban setting. The results of this study will fill a critical gap in understanding urban malaria epidemiology and promote data-driven decision-making to ensure malaria control strategies are appropriate and can adapt to the local context.