Objective: This article puts forward consensus recommendations from PROSEC North America regarding single indirect restorations made from ceramic and nonmetallic biomaterials in posterior teeth. Overview: The consensus process involved a multidisciplinary panel and three consensus workshops. A systematic literature review was conducted across five databases to gather evidence. The recommendations, informed by findings from systematic reviews and formulated based on a two-phase e-Delphi survey, emphasize a comprehensive treatment strategy that includes noninvasive measures alongside restorative interventions for managing dental caries and tooth wear. The recommendations advocate for selecting between direct and indirect restorations on a case-by-case basis, favoring inlays and onlays over crowns to align with minimally invasive dentistry principles. The recommendations highlight the critical role of selecting restorative biomaterials based on clinical performance, esthetic properties, and adherence to manufacturer guidelines. They emphasize the importance of precision in restorative procedures, including tooth preparation, impression taking, contamination control, and luting. Regular follow-up and maintenance tailored to individual patient needs are crucial for the longevity of ceramic and nonmetallic restorations. Conclusions: These PROSEC recommendations provide a framework for dental practitioners to deliver high-quality restorative care, advocating for personalized treatment planning and minimally invasive approaches to optimize oral health outcomes. Clinical Significance: The PROSEC North America recommendations highlight the importance of minimally invasive techniques in posterior tooth restorations using ceramic and non-metallic biomaterials. These principles prioritize tooth structure conservation and personalized treatment planning, essential for enhancing clinical outcomes and long-term oral health.