Introduction: Drugs and substance abuse is one of the most pervasive problems in Kenya placing a great economic, social, and health burden on the society. If left unaddressed, the country risks losing generations and development opportunities due to the diversion of resources to address the problem. Therefore in lieu of the complexities of drugs and substance abuse, difficulties, and cost of treatment, the development of effective treatment and prevention programs is a crucial part of a public health system. This study sought to identify strategies that can be embedded in the health systems framework of Kenya for the prevention and management of drug and substance abuse. Methods: The paper reports qualitative findings from a cross-sectional mixed method study conducted between 2017 and 2018 in four counties; Isiolo, Kajiado, Murang’a, and Nyamira selected following a review of Kenya Medical Research Institute (KEMRI) Cluster Coordinators’ reports of priority research needs. Separate in-depth interviews were conducted with purposively selected; previous abusers (64), current abusers (127), opinion leaders (64), county officials (21), and health workers (64). Data was transcribed, translated, and analysed manually by identified thematic areas and by a statistical computer package, QSR NVIVO 12. Results: The identified strategies were: self-driven, social support, law enforcement, and rehabilitation. Self-driven strategies reported were; reduced consumption, keeping busy and off a bad company with highlighted challenges of; peer pressure, withdrawal symptoms, and idleness. The respondents suggested withdrawal management, job creation and counselling as measures to curb abuse of drugs and substances. Social support through love, acceptance, and social protection provided by family, community, faith-based, and non-governmental organisations was reported as helpful amid challenges such as stigma, familial problems, and joblessness. Awareness creation, counselling and economic empowerment were mentioned as important for social support. Law enforcement through arrests, prosecution, and disruption of drug distributions was reported as an important strategy with barriers related to corruption, poor community-police relationships, and lack of clear laws being highlighted. Opportunities for addressing the barriers included; community involvement, stakeholders’ partnerships, and devolving National Authority for the Campaign Against Alcohol and Drug Abuse (NACADA) functions. Rehabilitation was another identified strategy with funding needed to provide adequate facilities and human resources to provide such services. Conclusion: The identified strategies are effective in the management and control of drug and substance abuse. However, a multi-sectoral approach is needed within the public healthcare system to curb the risk of social, economic and health crises related to drugs and substance abuse in Kenya.