With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases., Competing Interests: Declaration of interests KK reports personal fees from Amgen, AstraZeneca, Bayer, NAPP, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Roche, Berlin-Chemie Menarini, Boehringer Ingelheim, Sanofi-Aventis, and Servier; other from AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi-Aventis; and grants from AstraZeneca, Novartis, Novo Nordisk, Sanofi-Aventis, Eli Lilly, Servier, Pfizer, Boehringer Ingelheim, and Merck Sharp & Dohme, outside the submitted work. VJ reports grants and personal fees from Baxter Healthcare, grants from NephroPlus, and personal fees from AstraZeneca, outside the submitted work. RGG reports grants or research support in the past 2 years from Gilead Sciences; consultancy or adviser roles in the past 2 years for Abbott, AbbVie, Access Biologicals, Antios, Arrowhead, Bayer, Bristol Myers Squibb, Dova, Dynavax, Eiger, Eisai, Enyo, eStudySite, Forty-Seven, Genentech, Genlantis, Gerson Lehrman, Gilead Sciences, HepaTX, HepQuant, Intercept, Janssen, Helios, Eli Lilly, Merck Sharp & Dohme, Salix, Shionogi, and Viking Therapeutics; current activity with scientific or clinical advisory boards for Abbott, AbbVie, Merck Sharp & Dohme, Arrowhead, Bayer, Dova Pharmaceuticals, Eiger, Enyo, Gilead Sciences, HepQuant, Intercept, Janssen, and Prodigy, outside the submitted work. RGG is a member of Topography Health clinical trials alliance; chair of the Prodigy Clinical Advisory Board; an advisory consultant for Biocollections, Fibronostics, Fujifilm/Wako, and Quest; and member of the data safety monitoring board for ArrowHead and CymaBay Therapeutics. RGG currently has consulting confidentiality agreements with AbbVie, Abbott, Access Biologicals, ADMA Biologics, AEC Partners, Aligos Therapeutics, Arena Pharmaceuticals, ArrowHead, Arterys, Alexion, Altimmune, Antios Therapeutics, AprosTx, Bayer, Cirina, Consumer Health Products Association, CymaBay Therapeutics, DiaSorin, Dova Pharmaceuticals, DRG Abacus, DURECT, Dynavax, Echosens, Eiger, Enyp, Exelixis, Fibronostics, Forty-Seven, Fujifilm Wako Diagnostics, Gilead Sciences, HepQuant, HepaTx, IDLogiq, Intellia, Intercept, Inotek, Iqvia, Janssen/J&J, KannaLife, Laboratory for Advanced Medicine, Labyrinth, Life Line Screening, Eli Lilly, MedImmne, Merck Sharp & Dohme, New Enterprise Associates, Ogilvy CommonHealth, Organovo, Patient Connect, Prodigy Biotech, Prometheus Laboratories, Refuah Solutions, Regulus Therapeutics, Salix, Shionogi, Spring Bank, and Trimaran. RGG reports activities for Speakers Bureau, focusing on hepatitis B virus, hepatitis C virus, and liver cancer, specifically epidemiology, diagnosis, and treatment, and programme presentations on vaccination for hepatitis B virus and management of complications of cirrhosis. RGG has a speaker's contract to do promotional talks for AbbVie, BMS, Eisai, Gilead Sciences, and Intercept. RGG is a minor stock shareholder (only for projects in the liver space but not fatty liver disease-related) for RiboSciences and CoCrystal. RGG holds stock options in Eiger, Genlantis, HepQuant, and AngioCrine. MHN reports grants from Glycotest, Gilead Sciences, Pfizer, Enanta Pharmaceuticals, BK Kee Foundation, National Cancer Institute, and Vir Biotechnology; and personal fees from Spring Bank, Novartis, Janssen Pharmaceuticals, Eisai, Bayer, Intercept, Exact Sciences, Laboratory of Advanced Medicine, Helios, and Eli Lilly, outside the submitted work. J-PD reports grants from Canadian Institutes of Health Research, outside the submitted work. JCGH reports personal fees from Novo Nordisk, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)