This monograph consists of five chapters that describe the diagnosis and treatment of oral squamous cell carcinoma (OSCC), which is the most common malignant epithelial neoplasm affecting the oral cavity. Chapter One deals with different potentially malignant disorders in the development of OSCC, diagnostic methods of OSCC, the pertinence of biomarkers in OSCC therapy, classification of biomarkers, existing biomarkers in different stages of OSCC and the challenges of developing new biomarkers. Chapter Two is focused on principles, systems, technologies, therapeutic approaches, safety and toxicity and patents comprising drug delivery systems for local oral squamous cell carcinoma treatment. Chapter Three aims to highlight a detailed critical review of previous literature on putative cancer stem cell pathways for oral carcinoma and draw interest in targeting the most common cancer stem cell markers as a therapeutic regimen for oral cancer preneoplastic tumours, metastasis, and treatment progression. Chapter Four aims to cover the recent developments in nanotechnology-based drug delivery systems, advanced nanomedicines and their diagnostics as well as therapeutic applications in OSCC. Finally, Chapter 5 aims to elaborate on the importance of biomarkers as an early diagnostic tool in detecting oral squamous cell carcinoma.