Syndromic surveillance has expanded since 2001 in both scope and geographic reach and has benefited from research studies adapted from numerous disciplines. The practice of syndromic surveillance continues to evolve rapidly. The International Society for Disease Surveillance solicited input from its global surveillance network on key research questions, with the goal of improving syndromic surveillance practice. A workgroup of syndromic surveillance subject matter experts was convened from February to June 2016 to review and categorize the proposed topics. The workgroup identified 12 topic areas in 4 syndromic surveillance categories: informatics, analytics, systems research, and communications. This article details the context of each topic and its implications for public health. This research agenda can help catalyze the research that public health practitioners identified as most important.