Background: Oral candidiasis is an opportunistic infection that is common among breast cancer patients who are under chemotherapy. The rising levels of fluconazole resistance in Candida albicans are a cause of concern in the context of the therapeutic effectiveness of this drug, especially in immunocompromised individuals. Nevertheless, there is limited knowledge of clinical-molecular studies on cancer in the Middle East. Methods: A prospective, case-control study took place in the period between 1 February 2024 and 4 June 2025 in the Dhi Qar Province, Iraq. A hundred patients with breast cancer (50-75 years) and 100 age-matched controls (healthy individuals) were recruited. Oral swabs had been cultured and isolates were characterized phenotypically and identified by ITS sequencing. Test was done on antifungal susceptibility as per CLSI M27-A3. ERG11, CDR1 and MDR1 expression were determined by RT-qPCR in accordance with MIQE. Sanger sequencing revealed ERG11 mutation as well. Independent predictors of fluconazole resistance were determined with the use of multivariable logistic regression. Results: Candida species were identified in 77 percent of the patients vs. 32 percent of the control group (p < 0.001). C. albicans comprised 75 per cent of isolates. The patient isolates exhibited a significant level of resistance of fluconazole compared to the controls (24.7% vs 6.3% p = 0.01). There was a significant overexpression of CDR1 (median 4.4-fold), MDR1 (3.2-fold), and ERG11 (2.2-fold) in the resistant C. albicans isolates compared with the susceptibles (p < 0.01). Fifty-four percent of resistant isolates were found to have ERG11 mutations. The biomass of biofilm were found to be significantly higher in resistant strains (p = 0.001). In the multivariate analysis, previous exposure to fluconazole (OR 4.7), high level of CDR1 expression (OR 5.4) and high biofilm production (OR 3.3) were found to be independent predictors of resistance. The predictive model was good in discrimination (AUC = 0.85). Conclusions: Efflux pump overexpression and, to a minor degree, ERG11 mutations are the major factors that result in fluconazole resistance in oral C. albicans breast cancer patients. The findings highlight the significance of the incorporation of molecular diagnostics in the antifungal stewardship programs in cancer centers.