IMCI-PLUS is an inter-disciplinary, Pan-African-EU research partnership, with emphasis on capacity strengthening and mutual learning, to improve management of pediatric lower respiratory tract infections (LRTI)–the leading cause of child morbidity and mortality in Sub-Saharan Africa (SSA)–by working towards the adoption of point of care lung ultrasound (PLUS) into healthcare policy and routine clinical practice. Current Integrated Management of Childhood Illnesses (IMCI) guidelines fail to differentiate between uncommon severe bacterial infections and more ubiquitous self-limited viral illnesses; inappropriate antibiotic use is thus widespread and a key driver of antimicrobial resistance. Equally, tuberculosis cases are missed. The World Health Organization has identified the rigorous evaluation of PLUS to treat children with LRTI as a research priority, especially its health/economic impacts and operational barriers. Including diverse settings within 3 SSA countries (Senegal, South Africa, Tanzania), IMCI-PLUS determines real-life health (antibiotic prescription and clinical outcomes) and economic (cost and cost-effectiveness) impact of integrating PLUS into LRTI management through a prospective randomised controlled trial, combined with evidence from implementation research among 8500 children. Stakeholder engagement to assess acceptability and feasibility informs a co-designed implementation package with key uptake barriers explored and addressed. A main barrier—healthcare provider skills gaps—is innovated through AI-enabled automated PLUS interpretation. IMCI-PLUS generates tailored clinical decision tools integrating PLUS to manage LRTI syndromes across a range of epidemiological and healthcare settings. A comprehensive, integrated translational research framework, focusing on mutual learning by involving stakeholders and patients meaningfully during all evidence generation and translation stages, enables adoption of research findings into policy and practice.