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Metropolitan Santo Domingo has accounted for a majority of reported malaria cases in the Dominican Republic in recent years. To inform malaria control and elimination efforts, a cross-sectional survey of malaria knowledge, attitudes, and practices collected 489 adult household-level questionnaires across 20 neighborhoods in the city's two main transmission foci, Los Tres Brazos (n = 286) and La Ciénaga (n = 203), in December 2020. Overall, most residents (69%) were aware of the problem of malaria in Santo Domingo, but less than half knew that mosquitos transmit the disease (46%) or took any correct preventative measure (45%). More residents of Los Tres Brazos, where malaria incidence is higher than in La Ciénaga, said that they had never been visited by active surveillance teams (80% versus 66%, respectively; P = 0.001), did not link mosquitos with malaria transmission (59% versus 48%, P = 0.013), and did not know medication can cure malaria (42% versus 27%, P = 0.005). Fewer residents of Los Tres Brazos said that malaria was a problem in their neighborhoods (43% versus 49%, P = 0.021) and fewer had mosquito bed nets in their homes (42% versus 60%, P < 0.001). The majority (75%) of questionnaire respondents in both foci did not have enough mosquito nets for all household residents. These findings demonstrate gaps in malaria knowledge and community-based interventions and highlight the need to improve community engagement for malaria elimination in affected areas of Santo Domingo.