This guidebook was prepared by TASC (The After-School Corporation) and their Frontiers in Urban Science Education (FUSE) programs. FUSE is TASC's initiative to help more out-of-school-time programs and expanded learning time schools offer kids engaging, exciting and inspiring activities that promote science inquiry. The guidebook offers a a framework and practical advice for creating and maintaining a high-quality science learning program at out-of-school time sites. The resources described herein can help increase student engagement in science using methods specifically designed for after-school settings. Updates in this second edition include a section on partnerships authored by staff from the New York Academy of Sciences, and new resources, like the ExpandED Schools family engagement guide, Click2SciencePD from the University of Nebraska and a checklist for helping programs assess their assets and constraints related to STEM, called the STEM Readiness Reflection. [The first edition of this guidebook was developed with support from the Noyce Foundation. Original text and materials for the first edition of this guidebook were provided by Rena Dorph and the Lawrence Hall of Science of the University of California, Berkeley. The Coalition for Science After School also provided information for the guidebook.]