A retrospective four-year study of the Plasmodium falciparum malaria and typhoid infection prevalence among the population strata instigates the evaluation of its implication on gender demography with speculated increase in morbidity and occasional mortality. The clinical implications of Plasmodium falciparum malaria and typhoid fever co-infection on gender demography and leukocyte pattern in hospital-based retrospective study were evaluated. Laboratory data of P. falciparum malaria and typhoid infection of patients attending a secondary hospital facility from 2020 till 2023 were retrieved and analyzed for estimated for the prevalence, distribution of P. falciparum malaria infection, and co-infection with typhoid fever. The retrieved patients’ data included their age, gender, and hematological parameters, P. falciparum malaria and typhoid fever results based on the result from blood samples analyzed for P. falciparum by rapid diagnostic test, blood film microscopy, and sero-detection by Widal reaction. For retrospective years examined for P. falciparum malaria positive, 48.4% (444/917), 46.2% (1061/2297), 47.9% (1067/2228), and 51.1% (1194/2335) were male patients compared to female subjects in 2020, 2021, 2022, and 2023, respectively. The co-infection rates of P. falciparum malaria and typhoid over the 2020–2023 years showed disproportionate rates among the gender distribution. Changes in leukocytes rates with yearly co-infection showed distribution of P. falciparum malaria and typhoid co-infection among male subjects with increasing rates of WBC, neutrophil, and lymphocytes while there is decreasing rates of PCV and monocytes as from year 2020 to 2023. There is no change in co-infection rates based on the median age. The prevalence rates of both malaria and typhoid co-infection would continue to increase over the years among the populace due to malaria endemicity and adequate laboratory diagnosis needed to be emphasized for these populations.