Prosthetic rehabilitation of a completely edentulous arch remains a significant clinical challenge. This case report presents the occlusal and prosthetic management of a completely edentulous maxilla opposing a partially edentulous mandible, a clinical situation at risk of developing combination syndrome. Favorable outcomes were achieved through early diagnosis and a systematic prosthetic approach. Careful treatment planning and strict adherence to the principles of fully balanced occlusion are essential to ensure stable, functional, and predictable results in patients related to Kelly’s syndrome.