Factors reported in the literature associated with inappropriate prescribing of antimicrobials include physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians’ decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing antimicrobials would minimize the risk of resistance and, consequently, improve patients’ clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. A cross-sectional study was conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed, validated, and piloted survey specific with closed-ended questions. A value of p < 0.05 was considered to be statistically significant. All data analysis was performed using the Statistical Package for Social Sciences (IBM SPSS version 23.0). 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All of the respondents acknowledged effectiveness, previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) as being key factors influencing physicians’ choice during antimicrobial prescribing. The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials were reported to be common practices. Furthermore, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials, and the use of antimicrobials without a physician’s prescription (i.e., self-medication) represent key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines.