This chapter examines the five essential macro-minerals, sodium, potassium, calcium, magnesium, and phosphorus, based on their physiological significance, dietary sources, absorption mechanisms, and systemic functions. These minerals are needed in moderate levels; however, they are crucial to bone metabolism, fluid management, acid-base balance, homeostasis, metabolic and neuromuscular activity, and the prevention of chronic diseases. The influence of modern diets on mineral status, along with the medical implications of their excesses and deficiencies, and a focus on WHO/FAO dietary recommendations are discussed. The chapter summarizes the increasing importance of mineral supplementation in immune system regulation, critical illness, and the prospective use of precision medicine in combination with personalized nutrition to maximize mineral intake for better health outcomes.