Background: Poor job satisfaction has been associated with less productivity and high staff turnover. Various factors are thought to contribute for job dissatisfaction among pharmacy professionals and very limited studies have been conducted in eastern part of Ethiopia. Therefore, the current study was aimed to assess the level of job satisfaction among pharmacy professionals and its predictors. Methods: A cross-sectional study was conducted among 232 pharmacy professionals to assess level of job satisfaction in public hospitals located in the eastern Ethiopia. The data were collected using self- administered semi-structured questionnaires. Data were entered into Epi-Data version 3.1 and exported to STATA version 14.2 for analysis. Associations between the dependent and independent variables were assessed by multivariate analysis using an Adjusted Odds Ratio (AOR) at a 95% confidence interval (CI) and p-value less than 0.05 was considered as significant. Results: A total 220 questionnaires were found complete and included in the analysis. The mean age of participants was 27.6(SD + 4.1). More than half of the respondents (55.4%) had a bachelor degree and the majority (86.4%) were working less than 40h per week, mostly in dispensing units (75.4%). About one third of the participants (32.7, 95% CI; 26.8–39.2) were found to be satisfied with their job. Age category of 20 to 25years in reference to age greater than 30years (AOR=3.5, 95% CI; 1.1–9.7), holding a bachelor degree in reference to having diploma (AOR=4.2, 95% CI; 1.8–10.00), working for more than 40h per week (AOR=6.2, 95% CI, 2.4–16), and working in dispensing units (AOR=2.4, 95% CI; 1.1–5.5) were found to have strong association with job dissatisfaction. Conclusion: In this study, the job satisfaction levels of pharmacy professionals were found to be very low. The age category of 20 to 25, holding a bachelor degree, working for more than 40h per week, and working in dispensing unit were found to be strong predictors of job dissatisfaction. Hence, pharmacy directors and hospital administrators should work to reduce unnecessary workload on the staffs and create good working climate.