Dengue, caused by the dengue virus (DENV), a member of the flavivirus family, continues to pose a significant threat to populations worldwide, despite advances in technology. Nearly half of the global population is at risk of contracting the disease, ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and Dengue Shock Syndrome (DSS). The precise mechanisms underlying the progression of DF to DHF and DSS remain unclear, and the presence of various DENV serotypes exacerbates this situation. Urbanization and climate change are expected to affect dengue epidemiology, potentially increasing the frequency and intensity of outbreaks. This review aims to consolidate the current knowledge on the biological characteristics, pathogenesis, and application of "Omics" based strategies for biomarker discovery for precision medicine. Although the precise mechanisms behind the progression from DF to DHF/DSS are not fully understood, hypotheses include immune over-activation, cytokine storms, and antibody-dependent enhancement. Studies of comorbid conditions have shown no significant association with the development of DHF/DSS in patients with diabetes, hypertension, or other chronic diseases. Despite the far-reaching and intricate nature of dengue, the inconsistencies found in clinical pathophysiological studies underscore the need for additional research aimed at elucidating the pathogenesis of DHF/DSS and devising effective preventive measures. Identifying the differentially expressed genes, proteins, and metabolites in DF, DHF, and DSS may enrich our understanding of the mechanisms underlying their pathogenesis. Moreover, these differentially regulated pathways may serve as novel therapeutic targets. These biomarkers may also be utilized for disease surveillance and the evaluation of the efficacy of therapeutic interventions for personalized treatment. Continuous research is essential to gain deeper insights into the mechanisms and progression of dengue fever and to formulate more effective prevention and control strategies. A multidisciplinary approach is vital for comprehending dengue virus pathogenesis, identifying risk factors, and creating targeted interventions, particularly through biomarker discovery using "Omics" approaches.