Abstract Background Knowledge is an important element in making decisions. Making decisions without having adequate knowledge will potentially lead to decision conflicts. This study aimed to analyze of preferences, trust, and interactions between nurses and parents as mediating between knowledge and shared decision-making in the care of newborns in hospitals. Methods The research design was descriptive cross-sectional study. The population was all parents of newborns hospitalized in Regional Hospital Jember Regency, East Java, Indonesia March–June 2021. The sampling method was selected by simple random sampling. The required participants are 92. Data collection by questionnaires compiled by researchers, and data analysis by Partial Least Square Structural Equation Modeling (PLS-SEM). Results The results showed that knowledge (T-statistics = 4.464; p = 0.000) influenced shared decision making through preferences (T-statistics = 3.600; p = 0.000), trust (T-statistics = 6.760; p = 0.000), and nurse interactions and parents (T-statistic = 9.160; p = 0.000). The interaction of nurses and parents proved to have the strongest influence on shared decision-making. This study recommends that nurses increase interaction with parents. Nurses can maximize the role of parents in together decision-making on the care of newborns in the hospital. Conclusion The knowledge influenced shared decision-making of newborn care through the preferences, trust, and interactions of nurses and parents. This study recommends that nurses should increase interaction with parents. Nurses can maximize the role of parents in shared decision-making on the care of newborns in the hospital.