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Globally, there are 2 billion 'informal' workers, who lack access to social protection while facing profound health risks and socioeconomic exclusions. The informal economy has generated most jobs in Low and Middle-Income Countries (LMICs), but few studies have explored informal workers' complex health vulnerabilities, including in the face of climate change. This paper will discuss recent action-research in Indore (India), Harare, and Masvingo (Zimbabwe) with informal workers like vendors, waste-pickers, and urban farmers. We conducted qualitative interviews (N = 110 in India), focus group discussions (N = 207 in Zimbabwe), and a quantitative survey (N = 418 in Zimbabwe). Many informal workers live in informal settlements ('slums'), and we highlight the interrelated health risks at their homes and workplaces. We explore how climate-related threats—including heatwaves, drought, and floods—negatively affect informal workers' health and livelihoods. These challenges often have gender-inequitable impacts. We also analyse workers' individual and collective responses. We propose a comprehensive framework to reveal the drivers of health in the informal economy, and we complement this holistic approach with a new research agenda. Our framework highlights the socioeconomic, environmental, and political determinants of informal workers' health. We argue that informal workers may face difficult trade-offs, due to competing priorities in the face of climate change and other risks. Future interventions will need to recognise informal workers' array of risks and co-develop multifaceted solutions, thereby helping to avoid such impossible choices. We recommend holistic initiatives to foster health and climate resilience, as well as participatory action-research partnerships and qualitative, intersectional data-collection with informal workers. • Climate change is exacerbating many risks to informal workers' health and livelihoods. • WASH access may foster gender equality and decent work, while tackling heat stress. • Policymakers can partner with informal workers to create inclusive, multi-pronged interventions. [ABSTRACT FROM AUTHOR]