This study investigates the unique interplay between thermal comfort and antimicrobial properties in base fabrics, shaping the foundation for the development of "Smart Socks" as advanced personal protective equipment (PPE). By delving into the inherent qualities of fibers such as cotton, polyester, bamboo, and wool and exploring fabric structures like single jersey, terry, rib, and mesh, the research captures the dynamic relationship between material composition and performance. Terry fabrics emerge as insulators, wrapping the user in warmth ideal for cold climates, while mesh structures breathe effortlessly, enhancing air circulation and moisture wicking for hot environments. Cotton mesh, with its natural affinity for moisture, showcases exceptional moisture management. Antimicrobial testing, focused on fabrics' interactions with Staphylococcus aureus, highlights the dormant potential of bamboo's bio-agents while revealing the necessity for advanced antimicrobial treatments. This study unveils a vision for combining innovative fabric structures and fibers to craft smart socks that balance thermal comfort, hygiene, and functionality. Future directions emphasize sensor integration for real-time physiological monitoring, opening pathways to revolutionary wearable PPE.