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Organizational change is a critical yet challenging process that often disrupts employee well-being, encompassing psychological, emotional, and physical dimensions. This study systematically reviews the impacts of organizational change on employee well-being, emphasizing the moderating roles of leadership, communication, and organizational culture. The findings highlight that uncertainty and ambiguity are primary stressors during transitions, leading to elevated levels of anxiety, burnout, and physical strain. However, transformational leadership and transparent communication significantly mitigate these adverse effects by fostering trust, emotional resilience, and adaptability among employees. Emotional well-being is particularly influenced by leadership behaviors, with empathetic and inclusive approaches shown to enhance morale and reduce resistance to change. Physical health outcomes, such as fatigue and stress-related illnesses, are exacerbated by prolonged transitions but can be alleviated through wellness programs and supportive leadership. The study also addresses contemporary challenges posed by digital transformations, emphasizing the dual role of technology as a stressor and enabler. Employees’ adaptability and digital literacy emerge as critical factors in navigating technological transitions, underscoring the need for targeted interventions. By integrating findings from diverse studies, this review provides a holistic understanding of employee well-being during organizational change. Practical recommendations include fostering transformational leadership, promoting inclusive workplace practices, and implementing comprehensive wellness initiatives. This research contributes to the existing literature by highlighting the interplay of individual, organizational, and technological factors, offering a foundation for future studies to explore long-term impacts and innovative strategies for managing change in evolving work environments.