Anthropogenic pressures on the Earth’s natural systems are mounting, which is having devastating consequences for human health, including an increased threat of mosquito-borne diseases. Climate variation and land-use change influence mosquito-borne disease risk by determining vector occurrence and distribution, in addition to vector-human contact rates. Despite an understanding of the mechanisms underlying the relationship between climate variation and mosquito-borne disease transmission, few studies have considered the impact of mediating and interacting factors. There is a growing need to understand the joint impact of climate variation and land-use alterations on the spatiotemporal variation of mosquito-borne diseases, in conjunction with socioeconomic factors such as vector control activities. In this thesis, I investigate how climate variation, land-use change and socioeconomic factors affect spatiotemporal disease risk by using an integrated modelling framework. I firstly investigate the joint influence of both climate variation and vector control activities on malaria incidence in a high-risk border region of Ecuador, using a Bayesian hierarchical mixed effects modelling framework to account for multiple risk factors (Chapter 2). I find a difference in both the effectiveness of control measures and the impact of climate variation on the two predominant malaria parasites, with P. falciparum demonstrating greater climate sensitivity than P. vivax malaria. I then test for the interacting effects of climate and land use on disease risk by investigating the synergistic effects of environmental degradation and climate variation on malaria re-emergence in southern Venezuela in Chapter 3. I show that the effect of temperature on malaria incidence is amplified in areas degraded by mining activity. Further, I demonstrate that the choice of climate data product used to inform climate-disease models has implications for the resulting associations between climatic variables and disease risk (Chapter 4). Finally, in Chapter 5 I investigate differing taxonomic mosquito responses to land-use change using a systematic data search strategy and comparative space-for-time approach. I find strong declines in species richness of both Aedes and Anopheles mosquitoes in urban environments, in addition to diverging species-specific abundance responses. I additionally discuss how climate-disease research can be intuitively integrated into policy-relevant impact assessments. In this thesis, I demonstrate how multiple components of mosquito-borne disease risk can be attributed to environmental change, advancing knowledge on how climate variation, land-use change and socioeconomic factors synergistically interact to determine mosquito-borne disease risk.