In Tasmania, a temperate island state of Australia, there is little understood about the human health implications of a changing climate. Here, we investigate the hypothesis that human populations in Tasmania might become more vulnerable to Ross River virus (RRV) under climate change, Australia’s most significant vector-borne disease. Importantly, our study considers the complex social-ecological systems based setting that this virus represents, with our approach being underpinned by systems thinking. Specifically, we undertake an integrated and participatory assessment of potential human vulnerability to RRV in a changing climate, and taking account of other parallel, non-climate regional-scale change considerations. We show that projected moderate changes in Tasmania’s climate will have implications for the State’s human health, whereby Tasmania is likely to become more vulnerable to RRV as the 21st Century progresses, shifting this health issue from a relatively low public health risk to one that will become more concerning and costly. The study assists us to contemplate how we frame human health questions as we move into a climatically changing world and reminds us that health impacts will not always be linear or obvious. It demonstrates an approach for scoping indirect and potentially insidious implications of climate change, even in the face of uncertainty, imperfect systems understanding, and limited resources, to inform a range of decision makers.