Background. Nepal faced a major dengue outbreak in 2022. The majority of hospitals and laboratories had limited resources for dengue confirmation and had to rely on rapid dengue diagnostic tests. The purpose of the study is to find the predictive hematological and biochemical parameters in each serological phase of dengue infection (NS1 and IgM) that may assist in dengue diagnosis, severity assessment, and patient management via the use of rapid serological tests. Method. A laboratory-based cross-sectional study was conducted among dengue patients. Rapid antigen (NS1) and serological test (IgM/IgG) was performed to diagnose positive dengue cases. Furthermore, hematological and biochemical investigations were carried out and compared between NS1 and/or IgM-positive participants. A logistic regression analysis was used to identify the validity of the hematological and biochemical characteristics for dengue diagnosis as well as patient management. Receiver-operating characteristic (ROC) curve analysis was used to define the best cut-off, sensitivity, and specificity. Result. Multiple logistic regression showed thrombocytopenia (ORA = 1.000; p = 0.006), leukopenia (ORA = 0.999;
p
<
0.001
), glucose level (ORA = 1.028;
p
=
0.029
), aspartate aminotransferase (ORA = 1.131;
p
=
0.001
), and monocytosis (ORA = 2.332;
p
=
0.020
) as significant parameters in the NS1-only positive group. Similarly, thrombocytopenia (ORA = 1.000;
p
=
0.001
), glucose level (ORA = 1.037;
p
=
0.004
), and aspartate aminotransferase (ORA = 1.141;
p
<
0.001
) were significant in IgM-only positive patients. Moreover, thrombocytopenia (ORA = 1.000;
p
<
0.001
), leukopenia (ORA = 0.999;
p
<
0.001
), glucose (ORA = 1.031;
p
=
0.017
), aspartate aminotransferase (ORA = 1.136;
p
<
0.001
), and lymphopenia (ORA = 0.520;
p
=
0.067
) were independent predictors in both NS1 + IgM positive groups. Platelets consistently demonstrated a higher area under the curve with increased sensitivity and specificity throughout all models, while aspartate aminotransferase (AUC = 0.811) and glucose (AUC = 0.712) demonstrated better results when single IgM positivity was observed. The total leukocyte count performed better when both NS1 + IgM were positive (AUC = 0.814). Conclusion. Hence, thrombocytopenia, elevated AST, high glucose level, leukopenia with monocytosis, and leukopenia with lymphopenia may predict dengue diagnosis and its severity during an active infection. Therefore, these laboratory parameters can be used to complement less sensitive rapid tests, improve dengue diagnosis, and help with proper patient management.