Background: Predominantly African American communities continue to experience challenges in cancer prevention, screening, and outcomes. This study explored perceptions, experiences, and challenges related to cancer prevention and screening among adults recruited through a community engagement initiative in a predominantly African American urban community in Houston, Texas. Methods: Four virtual focus groups were conducted between May 2021 and August 2022 with 35 participants. Sessions addressed prostate cancer, breast cancer, and general cancer prevention. Transcripts were analyzed using thematic analysis, and findings were reported in accordance with COREQ guidelines. Final themes were interpreted using the Socioecological Model. Results: Four interconnected themes reflected individual/interpersonal, healthcare/organizational, community, and structural/policy factors: (1) personal and family experiences and social support; (2) healthcare experiences and trust; (3) structural and financial challenges; and (4) community engagement, education, and advocacy. Family support, trusted providers, community resources, and culturally relevant education facilitated prevention engagement, while negative healthcare experiences, insurance restrictions, costs, and complicated healthcare navigation created challenges. Conclusions: Cancer prevention engagement was shaped by interacting influences across socioecological levels. Multilevel, culturally responsive approaches that strengthen trust and community partnerships while addressing financial, healthcare access, and structural challenges may improve cancer prevention and screening engagement.