 The paper highlights that despite the proliferation of eHealth interventions, underserved groups do not benefit proportionately due to usability issues and lack of attention to broader structural barriers. The authors draw lessons from their experience in designing user-centered eHealth interventions over 15 years at the Dana-Farber Cancer Institute and Harvard T.H. Chan School of Public Health, focusing on three projects that used web portals and health apps targeted toward underserved groups. They distilled five key principles for researchers aiming to design eHealth interventions for underserved groups, developing a strategic roadmap, engaging multiple stakeholders, designing with usability in mind, building privacy safeguards, and striving for an optimal balance between open science aspirations and protection of underserved groups. This article was authored by Edmund W. J. Lee, Rachel F. McLeod, and Kasisomayajala Vishwanath.