Background Dengue fever significantly burdens healthcare systems, particularly in resource-limited settings such as Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan. Mufti Mehmood Memorial Teaching Hospital, the designated Dengue Isolation Unit in the region, continues to receive a steady influx of patients. This study analyzed the epidemiological profile of dengue cases admitted to the hospital to support public health planning and guide resource allocation. Methods This retrospective study was conducted at Mufti Mehmood Memorial Teaching Hospital, Dera Ismail Khan, from October to December 2024, following ethical approval from the Institutional Review Board. A total of 168 patients with confirmed dengue fever (based on positive non-structural protein 1 (NS1) antigen or immunoglobulin M (IgM)/immunoglobulin G (IgG) antibody tests) were included. The hospital also serves neighboring districts, covering a combined population of over 4.2 million. Patients with co-infections (e.g., malaria, typhoid, or leptospirosis) or without consent were excluded. Data were collected using a structured abstraction form and included demographic variables (age, gender, district of residence), clinical features (fever, body aches, hemorrhagic signs, skin rash), epidemiological information (recent travel history and destination), and laboratory findings (NS1 antigen or IgM/IgG results). Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0 (Released 2018; IBM Corp., Armonk, NY, US). Associations between categorical variables were tested using the chi-square test, with p-values less than 0.05 considered statistically significant. Grammar was checked using Grammarly software (Grammarly, Inc., San Francisco, CA). Results Among the 168 patients diagnosed with dengue virus infection, 137 (81.5%) were male and 31 (18.5%) were female. The mean age was higher among females (34.5 ± 13.5 years) than males (28.0 ± 10.6 years), indicating more age variability in female patients. The most affected age group was 16-30 years (n = 101, 60.1%), followed by 31-45 (n = 44, 26.2%). Cases rose progressively from October (n = 37, 22%) to a peak in November (n = 108, 64.3%), before declining in December (n = 23, 13.7%). Serological testing showed full positivity for NS1, IgM, or IgG in all female patients. In contrast, a few male patients were negative for at least one marker (NS1, 4/137; IgM, 13/137; IgG, 9/137), though these differences were not statistically significant. Similarly, no significant gender-based differences were observed in clinical features such as fever, body aches, bleeding, or rashes. Most patients (n = 114, 67.9%) reported no recent travel history, while 54 (32.1%) had travelled to Karachi, Islamabad, or Rawalpindi. The highest number of cases originated from District Tank (n = 63, 37.5%), followed by Lakki Marwat (n = 46, 27.4%) and Dera Ismail Khan (n = 44, 26.2%). Conclusion Dengue fever peaks during the post-monsoon season and disproportionately affects males and young adults. District Tank and Lakki Marwat reported the highest burden of disease. Poor sanitation and limited mosquito control appear to drive transmission. These findings underscore the need for targeted vector control measures, public health awareness campaigns, and strengthened healthcare infrastructure to manage future outbreaks more effectively.