Dengue is a mosquito-transmitted virus, with a human burden approaching 400 million infectionsannually. Zika virus transmission has exploded in the path of dengue, since they share the Aedes aegypti mosquito as the primary vector. There is an urgent need for developing effective local and global strategies for control and prevention of both dengue and Zika. The World Health Organization described dengue as the most widespread arthropod-borne viral infection in the world. The reasons for its dramatic expansion in recent years as well as the cyclic temporal pattern and varying spatial pattern of incidence in endemic regions are not fully understood. Factors underlying the rapid expansion of dengue take on a deeper importance in the context of the recent emergence of Zika. The timing of epidemics and spatial- extent of diseases such as dengue and Zika that result from transmission between humans and mosquitoes are regulated by weather in complicated ways. Weather regulates transmission-potential via its effects on vector dynamics. For Aedes aegypti mosquitoes, slight changes in different components of weather have important effects on population dynamics, lifespan, biting-frequency, virus incubation period and capacity to transmit the virus, thus inducing changes in transmission probability. These complicated dynamics produce a weather-disease connection that is not well-defined for different ecological settings. Understanding this connection is important to critical elements of policy development and operational control of dengue such as predicting risk, developing human-vector transmission models, and planning effective surveillance-intervention strategies. An important gap in understanding risk and roadblock in model development is an empirical perspective clarifying how weather impacts vector dynamics in diverse ecological settings. Studies of the weather-disease connection based on empirical data from Thailand and Peru provided a profile of how weather regulates disease (via vector dynamics) across diverse transmission settings. We sought to determine if location, timing, and potential-intensity of dengue virus transmission is systematically defined by weather. Results showed that temperature defined a viable range for transmission; however, humidity amplified the potential within that range. This duality is assumed to be fundamental to risk. Transmission-potential is regulated by temperature-humidity coupling, enabling epidemics in a limited and specific area of weather-space. In a novel modeling framework, a high-resolution, spatially-explicit, individual-based approach to modelling mosquito-human dengue virus transmission across entire countries was developed and applied to understanding the theoretical basis for observed disease patterns and to develop tools for estimating risk and effective risk reduction strategies. The SEIRscape framework was configured to simulate dengue virus transmission across Thailand and Peru. Estimates of the vector basis of risk mirrored observed disease patterns across both countries at high resolution and enabled virtual intervention trials for risk reduction. SEIRscape represents a new conceptual approach to modelling virus transmission that allows examination of the effects of heterogeneity in risk across a broad range of spatial scales.