Priority setting, or determining how to best allocate limited resources, is an important first step for evidence-based public health approaches in community-based organizations (CBOs), but guidance for such work is limited. This study aims to study drivers of priority setting and the way CBOs use data for this work. Data come from PLANET MassCONECT, a Community-Based Participatory Research project focused on knowledge translation among CBOs targeting the underserved in Boston, Lawrence, and Worcester, MA. We conducted four focus group discussions with CBO staff members (31 participants) in 2008 and a survey of 214 CBO staff members in 2009. Multiple, often competing factors appear to drive priority setting, including data, funding, partnerships, and community preferences. The process may be hindered by challenges related to finding, evaluating, and utilizing data for priority setting. Supporting CBOs in efforts to use data effectively and incorporate context into systematic priority-setting processes is vital.