BACKGROUND: People with severe mental disorders (SMD) experience premature mortality mostly from preventable physical causes. The World Health Organization (WHO) have recently produced guidelines on the management of physical health conditions in SMD. This paper presents the evidence which led to the recommendations for tobacco cessation and management of substance use disorders in SMD. METHODS: Scoping reviews informed 2 PICO (Population Intervention, Comparator, Outcome) questions relating to tobacco cessation and management of substance use disorders in SMD. Systematic searches led to the identification of systematic reviews with relevant evidence to address these questions. Retrieved evidence was assessed using GRADE methodology, informing the development of guidelines. RESULTS: One thousand four hundred thirty-four records were identified through systematic searches for SMD and tobacco cessation, of which 4 reviews were included in GRADE tables and 18 reviews in narrative synthesis. For SMD and substance use disorders, 4268 records were identified, of which 4 studies from reviews were included in GRADE tables and 16 studies in narrative synthesis. People with SMD who use tobacco should be offered combined pharmacological (Varenicline, Bupropion or Nicotine Replacement Therapy) and non-pharmacological interventions such as tailored directive and supportive behavioural interventions. For people with SMD and substance use disorders (drug and/or alcohol), interventions should be considered in accordance with WHO mhGAP guidelines. Prescribers should note potential drug-drug interactions. Recommendation were conditional and based on low/very low certainty of evidence with a scarcity of evidence from low- and middle-income settings. CONCLUSIONS: These guidelines mark an important step towards addressing premature mortality in people with SMD. The dearth of high-quality evidence and evidence from LMIC settings must inform the future research agenda. GUIDELINES: https://www.who.int/mental_health/evidence/guidelines_physical_health_and_severe_mental_disorders/en https://www.who.int/publications-detail/mhgap-intervention-guide%2D%2D-version-2.0.