Menstrual health and hygiene are a major public health and social issues in Nepal. Due to inadequate infrastructure to provide education, healthcare, and communication as well as religious teachings, women and girls are excluded from participation in many activities of daily living and community activities during menstruation. Evidence based research addressing menstrual health and hygiene in Nepal is scares. The objective of this paper is to review the current state of knowledge on menstrual health and hygiene in Nepal through a socio-ecological perspective. This systematic review identifies knowledge gaps and targets for future research and interventions. Studies from Nepal that examined factors contributing to menstrual health and hygiene were identified through searches across six databases (Medline, CINAHL, Web of Science, PsychInfo, Nepal Journals Online and Kathmandu University Medical Journal) in January 2019. The SEM is a public health framework that describes how health is impacted at multiple levels including the individual, interpersonal, community, organizational and policy levels. Key themes were identified, and factors contributing to menstrual health and hygiene were categorized as per the level of socio-ecological model (SEM). After a comprehensive literature review, twenty peer-reviewed publications, published between 2003 and January 2019 were included in this review. Eighteen studies were descriptive and two were interventional. The main outcomes reported were reproductive health concerns and menstrual hygiene practices. Nine studies focused on knowledge, attitude, and practices regarding menstruation, seven studies highlighted reproductive health issues, three studies focused on prevalence of culturally restrictive practices, and one on school absenteeism and intimate partner violence. Lack of awareness regarding menstrual health and hygiene, inadequate WASH facilities, no sex education and culturally restrictive practices makes menstruation a challenge for Nepali women. These challenges have negative implications on women and girls’ reproductive as well as mental health and school attendance among adolescent girls. There are gaps in the evidence for high quality interventions to improve menstrual health and hygiene in Nepal. Future research and interventions should address needs identified at all levels of the SEM.