ABSTRACT Background: Collection and compilation of spatial, meteorological, entomological, and virological data are critical in mitigating climate-sensitive emerging infections like dengue. This study was a holistic attempt to understand the dengue situation in the Kasaragod district of Kerala, India. Methods: This cross-sectional study was conducted in 13 health institutions from June to July 2021. Adult patients presenting with fever and testing positive for NS1 ELISA were subjected to Dengue RT-PCR and serotyping. The spatial and clinical features of the RT-PCR-positive patients, the district’s meteorological data, and the vector indices were studied. Results: The pre-epidemic months were marked by intermittent rainfall, peak ambient temperature and high larval indices. Among the 136 dengue RT-PCR patients studied, 41.2% had DENV2 followed by DENV1 (22.8%), DENV3 (5.9%) and DENV4 (4.4%); with 25% mixed infections. DENV1 showed a higher risk of gastrointestinal manifestations (80.6%, p=0.019) and musculoskeletal symptoms (77.4%, p=0.026) compared with other serotypes. Conclusions: In the context of dengue hyperendemicity, the possibility of an emerging serotype’s dominance coupled with the mixing up of strains should warn the health system regarding future outbreaks. Furthermore, the study emphasizes the importance of monitoring larval indices and the window of opportunity to intervene between environmental predictors and dengue outbreaks.