The Sierra Nevada de Santa Marta (SNSM) is a mountainous area in Colombia that is highly endemic to Chagas disease. We explored some eco-epidemiological attributes involved in the Chagas disease transmission scenario in three Indigenous communities. An epidemiological survey was done, where parasite infection in reservoirs and insects, Trypanosoma cruzi genotyping, identification of blood-meal sources in intradomiciliary insects using the high-resolution melting technique, and some risk factors were evaluated. The results suggest that several dwelling conditions such as thatched palm roofs and mud walls carried the highest risk of finding intradomiciliary Rhodnius prolixus , which 56.41% were infected with T. cruzi and fed with human blood. Moreover, T. cruzi Ia was the most frequent haplotype found in insects. These results indicate the existence of a domestic T. cruzi transmission cycle that does not overlap with the sylvatic cycle, and highlight the need for efficient entomological control focused to this area.