Background: The rising incidence of resistant fungal infections poses significant therapeutic challenges. This study aimed to compare the efficacy and safety of terbinafine monotherapy versus combination therapy with terbinafine and voriconazole in patients with resistant fungal infections. Methods: A total of 90 participants were enrolled from June 2022 to May 2024 at Colonel Maleque Medical College, Manikgonj, Bangladesh. Participants were randomly assigned to receive either terbinafine (6 mg/kg, maximum 500 mg/day) alone or in combination with voriconazole (200 mg/day). Outcomes assessed included mycological cure rates, clinical improvement, relapse rates, and adverse events over a 1-year follow-up period. Results: At 6 weeks, the mycological cure rate was 44% for the monotherapy group versus 78% for the combination group (p=0.001). At 1 year, the rates were 29% and 67%, respectively (p=0.001). Complete clinical improvement was observed in 29% of monotherapy patients compared to 62% in the combination group (p=0.002). Adverse events were more common in the combination group (44% vs. 22%, p=0.03), including higher rates of liver enzyme elevation and visual disturbances. Relapse rates at 1 year were lower in the combination group (27% vs. 44%, p=0.05). Conclusion: Combination therapy with terbinafine and voriconazole significantly improves mycological cure rates and clinical outcomes in resistant fungal infections compared to monotherapy, despite an increased incidence of adverse events.