Hand, foot, and mouth disease (HFMD) has threatened East Asia for more than three decades and has become an important public health issue owing to its severe sequelae and mortality among children. The lack of effective treatment and vaccine for HFMD highlights the urgent need for efficiently integrated early warning surveillance systems in the region. In this study, we try to integrate the available surveillance and weather data in East Asia to elucidate possible spatiotemporal correlations and weather conditions among different areas from low to high latitude. The general additive model (GAM) was applied to understand the association between HFMD and latitude, as well as meteorological factors for islands in East Asia, namely, Japan, Taiwan, Hong Kong, and Singapore, from 2012 to 2014. The results revealed that latitude was the most important explanatory factor associated with the timing and amplitude of HFMD epidemics (P < 0.0001). Meteorological factors including higher dew point, lower visibility, and lower wind speed were significantly associated with the rise of epidemics (P < 0.01). In summary, weather conditions and geographic location could play some role in affecting HFMD epidemics. Regional integrated surveillance of HFMD in East Asia is needed for mitigating the disease risk.