Many coastal communities rely on living marine resources for livelihoods and food security. These resources are commonly under stress from overfishing, pollution, coastal development and habitat degradation. Climate change is an additional stressor beginning to impact coastal systems and communities, but may also lead to opportunities for some species and the people they sustain. We describe the research approach for a multi-country project, focused on the southern hemisphere, designed to contribute to improving fishing community adaptation efforts by characterizing, assessing and predicting the future of coastal-marine food resources, and co-developing adaptation options through the provision and sharing of knowledge across fast-warming marine regions (i.e. marine ‘hotspots’). These hotspots represent natural laboratories for observing change and concomitant human adaptive responses, and for developing adaptation options and management strategies. Focusing on adaptation options and strategies for enhancing coastal resilience at the local level will contribute to capacity building and local empowerment in order to minimise negative outcomes and take advantage of opportunities arising from climate change. However, developing comparative approaches across regions that differ in political institutions, socio-economic community demographics, resource dependency and research capacity is challenging. Here, we describe physical, biological, social and governance tools to allow hotspot comparisons, and several methods to evaluate and enhance interactions within a multi-nation research team. Strong partnerships within and between the focal regions are critical to scientific and political support for development of effective approaches to reduce future vulnerability. Comparing these hotspot regions will enhance local adaptation responses and generate outcomes applicable to other regions.