SUMMARY The Systems Approaches to Cancer Biology (SACB) meeting aims to bring together scientific leaders and early-stage investigators in Cancer Systems Biology to build and foster a thriving and collaborative field by sharing scientific advances. Started as a grassroots effort from early-stage Cancer Systems Biology investigators, the first SACB meeting was held in 2016 and is held every other year. SACB has been sponsored by the National Cancer Institute and continues to be sponsored by the Association for Cancer Systems Biologists (ACSB). The meeting is solely focused on research topics that address cancer as inherently complex, with spatial, temporal, and interpatient heterogeneity, and with multifactorial causes and consequences that cannot be understood without integrating diverse approaches from a combination of traditional scientific disciplines. The SACB meeting consists of six plenary sessions, as well as poster sessions, special topic sessions, and many opportunities for early-stage investigators to network and gain mentorship from more senior investigators. SACB plenary sessions focus on many aspects of cancer biology and cover a diversity of computational/mathematical modeling approaches. This problem-domain-focused (as opposed to methods-focused) programming is particularly conducive to the synthesis of new ideas and collaborations among attendees. Given the history of this meeting, there is a strong emphasis on the development and fostering of early-stage investigators, which includes at least half of the oral presentations being given by trainees and addressing topics of interest to early-stage investigators through special topic sessions. Another focus of the meeting is to grow the Cancer Systems Biology community, which we will accomplish by targeting underserved research communities and reaching out to researchers in complementary topic areas, such as computer science or engineering. We will also provide funding support for early-stage investigators to attend the meeting, as well as funding support for investigators with additional family needs. SACB has successfully helped to advance the careers of many early-stage investigators and brings together like-minded scientists to share research findings. Moving forward, and building on a very successful virtual meeting in 2020, SACB will become a hybrid meeting, with both in-person and virtual meeting options. This will provide a venue for SACB to reach colleagues across the world and still be able to provide the intimate environment needed to foster Cancer Systems Biology research into the future.