Background: Acne vulgaris affects millions worldwide, with psychological stress emerging as a significant contributor to its development. Stress influences acne via hormonal fluctuations, inflammation, immune modulation, altered skin barrier function, and lifestyle changes. Understanding these mechanisms is crucial for developing effective management strategies. This study aims to elucidate the role of stress in acne pathogenesis to inform more targeted interventions.Methods: A comprehensive search encompassing databases such as PubMed, MEDLINE, Google Scholar, open access / subscription-based journals, was conducted to retrieve relevant articles for the investigation of key mechanisms through which stress impacts acne development and exacerbation. Articles were searched without any date restrictions. Utilizing the criteria delineated in the methodology section, studies were systematically reviewed to elucidate the relationship between psychological stress and acne development and exacerbation. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).Results: Our investigation revealed multiple key mechanisms through which stress impacts acne development and exacerbation. Hormonal fluctuations, including increases in cortisol and androgens, stimulate sebaceous gland activity, leading to excess sebum production. Inflammation, triggered by stress-induced cytokine release, exacerbates acne lesions. Stress also impairs skin barrier function, alters immune responses, and influences lifestyle factors such as diet, sleep, and skincare habits, all of which contribute to acne severity. Additionally, neuropeptides, oxidative stress, insulin resistance, altered skin pH, vascular changes, and changes in the skin microbiome play significant roles in stress-induced acne pathogenesis. These findings highlight the varied nature of stress-acne interactions and underscore the importance of addressing both physiological and psychological factors in acne management strategies.Conclusion: Our investigation reveals stress's varied impact on acne through hormonal fluctuations, inflammation, barrier function impairment, immune modulation, behavioral factors, psychological distress, neuropeptides, oxidative stress, insulin resistance, altered skin pH, vascular changes, lifestyle habits, and skin microbiome alterations. Addressing these mechanisms underscores the need for holistic acne management strategies integrating stress reduction techniques with conventional treatments. Understanding stress-acne interplay emphasizes the importance of comprehensive approaches to improve acne outcomes, recognizing the bidirectional relationship between physiological and psychological factors in acne pathogenesis and exacerbation.