Background: Healthcare professionals (HCPs) are particularly vulnerable to musculoskeletal disorders (MSDs) due to job demands such as prolonged standing, patient handling, and awkward postures. Objectives: This study aimed to assess the prevalence of MSDs among HCPs, examine the association between ergonomic knowledge and practices with MSDs, and identify predictors of ergonomic knowledge. Methods: A cross-sectional study was conducted among HCPs, including doctors and nurses, working in the United Arab Emirates (UAE). The prevalence of MSDs was determined using the Nordic Questionnaire. Ergonomic knowledge and practice were assessed through a validated questionnaire covering sociodemographic and work-related factors, ten knowledge items, and fifteen practice items. A scoring system was used, where correct answers received a score of one, and incorrect answers received a score of zero. Ergonomic knowledge and practices were considered inadequate when participant scores fell below the median values of six for knowledge and eight for practice. The calculated sample size was 398, with a response rate of 96%, resulting in 380 participants. The chi-square test, binary, and multivariable logistic regression analyses were performed. Results: The twelve-month prevalence of MSDs was 90.4%, with the highest percentage reported in the lower back (56%), followed by the upper back (43.4%), neck (39.2%), shoulder (38.9%), and elbow (21.3%). Inadequate ergonomic knowledge and incorrect ergonomic practices were found in 61.8% and 36.3% of HCPs, respectively. A significant association was observed between inadequate ergonomic knowledge (P < 0.001) and practice (P = 0.035) and the presence of MSDs. Significant predictors of inadequate ergonomic knowledge included the number of years worked (OR: 1.9; 95%CI: 1.00 - 3.5, P = 0.049), the provision of ergonomics training and awareness at the workplace (OR: 3.7; 95%CI: 1.9 - 7.2, P < 0.001), and inadequate ergonomic practices (OR: 1.9; 95%CI: 1.1 - 3.0, P = 0.014). Conclusions: A very high prevalence of MSDs was found among HCPs, with the lower back being the most commonly affected site. Significant predictors of inadequate ergonomic knowledge included the number of years worked, the availability of ergonomics training at the workplace, and inadequate ergonomic practices. This study underscores the need for ergonomic training programs and ergonomically friendly workplaces to equip HCPs with the knowledge and practices necessary to prevent MSDs.