The workplace represents a relevant source of stress for workers, being a risk factor for many mental disorders and psychological difficulties, including burn-out syndrome. Healthcare workers and other help-professions are particularly susceptible to work-related stress. The present systematic review aims to (1) identify available interventions for managing workplace-related stress symptoms; (2) assess their efficacy; and (3) discuss the current limitations of available interventions. A systematic review has been conducted, searching on PubMed, APA PsycInfo, and Scopus databases. Eighteen papers have been identified, which included different interventions for the management of work-related stress in healthcare professionals. These approaches can be grouped as follows: (1) interventions focusing on the individual level using cognitive-behavioral therapy (CBT) approaches; (2) interventions focusing on the individual level using relaxation techniques; and (3) interventions focusing on the organizational level. As regards interventions targeting the individual level using CBT approaches, mindfulness-based interventions were effective in reducing levels of burn-out, stress, and anxiety and in improving quality of life. As regards intervention using relaxation techniques, including art therapy, Emotional Freedom Techniques (ECT) and brief resilience retreats had a positive effect on the levels of anxiety, stress, and burnout. As regards interventions at the organizational level, we found no evidence for supporting its effectiveness in reducing the levels of burnout. Furthermore, available studies are heterogeneous in terms of assessment tools, target populations, and type of interventions, which limits the generalizability of findings.