A major earthquake in 2015 that struck Nepal created a favorable environment for the rapid spread of infectious diseases. In anticipation of a cholera outbreak in 2016, UNICEF, Johns Hopkins University, and the Group for Technical Assistance, Nepal, collaborated to assist the government of Nepal to strengthen early warning surveillance, laboratory-based diagnosis, and field investigation. This article outlines the challenges and lessons learned in cholera prevention and control based on the authors' experiences in 2016. Priorities for the future plan should include sustaining the enhanced surveillance system for acute gastroenteritis and cholera, rolling out a rapid diagnostic test, and ensuring rapid and systematic epidemiological investigation and environmental testing.