Preparing students to succeed in college and careers requires aligned systems that allow for smooth transitions between institutions as well as integrated supports to enable learners to progress toward careers. Student transitions from secondary to postsecondary education and/or careers have long been stumbling blocks because preschool through Grade 12 (P-12) systems of education, institutions of higher education, and workforce stakeholders generally lack alignment in their expectations and supports for the learners with whom they interact. One of the most effective levers for facilitating transitions across institutions is aligning systems through collaboration. It is therefore essential that before embarking on collaborative efforts to address college and career readiness issues, states take time to carefully consider the collaborative purpose, the participating stakeholders, and the practical considerations for implementation and accountability that have the greatest potential to ultimately foster collaborative success. The guiding questions in this guide are designed to help states explore the complex challenges inherent in facilitating cross-systems alignment through ongoing collaboration. Each question borrows from the systems research base derived from within and outside the field of education. The key considerations that accompany each question are designed to help users frame their own efforts within the conditions that the research base links to collaborative success. Appendix A provides a deeper exploration of the research base and highlights state examples of how the key considerations can lead to successful collaborative work. Although collaboration across systems can be challenging, the questions and key considerations provided can help states foster meaningful relationships and connections with the ultimate goal of ensuring that all students are prepared for postsecondary success.