Antibiotic resistance associated with Multidrug-Resistant Organisms (MDRO) in nosocomial infections has evolved into an increasingly complex global health threat and has generated serious implications for the effectiveness of modern healthcare systems. This study aimed to examine a prevention model integrating clinical pharmacy education and Islamic medical ethics within the Malay Archipelagic Community, encompassing the Riau Islands, eastern coast of Sumatra, Johor, and Lingga Islands. The research employed a quantitative cross-sectional design using Structural Equation Modeling involving 412 respondents, comprising 187 clinical pharmacy personnel (45.4%), 163 hospitalized patients (39.6%), and 62 Islamic religious leaders (15.0%), across four geographical areas. The findings demonstrated that clinical pharmacy education was positively associated with MDRO prevention behavior (β = 0.61, p < 0.001), while the model explained 67.3% of the variance in prevention behavior (R² = 0.673). The model demonstrated acceptable fit (CFI = 0.96, RMSEA = 0.048, TLI = 0.94). Multi-group analysis further showed that the association between clinical pharmacy education and MDRO prevention behavior was stronger among respondents with higher Islamic medical ethics scores (β = 0.74) than among those with lower scores (β = 0.48; Δβ = 0.26, p = 0.001). These findings support the integration of clinical pharmacy education and culturally relevant Islamic ethical values as a contextual approach to strengthening MDRO prevention behavior in Malay Muslim communities. Hospitals serving Malay Muslim communities may therefore consider incorporating Islamic medical ethics into clinical pharmacy education and antimicrobial stewardship initiatives to strengthen culturally responsive MDRO prevention strategies.