Vitamin D3 deficiency has become a widespread global health issue affecting multiple physiological functions and contributing to numerous medical conditions such as musculoskeletal pain, fatigue, immune dysfunction, metabolic disorders, cardiovascular disease, and cognitive disturbances. In this systematic review, we discuss the cause, symptoms, and treatment of Vitamin D3 deficiency utilizing PRISMA guidelines by the analysis of 50 relevant studies. Insufficient sunlight exposure, inadequate dietary intake, metabolic disorders, and genetic predispositions are largely responsible for its wide occurrence. Low levels have been associated with an increased risk of osteoporosis, autoimmune disorders, insulin resistance, and mental health disorders, highlighting the need for early diagnosis and treatment. Strategies to mitigate risk include dietary changes, Vitamin D3 supplementation, lifestyle change, and focused medical treatment, this is supported by studies indicating personalized medicine may aid in determining optimal treatment based on genetic predisposition. Public health policies, food fortification, and awareness campaigns play an important role in reducing the global burden of vitamin D3 deficiency. Future studies should also investigate long-term health consequences, optimal dosing protocol, and interactions with other micronutrients, leading to better and long-lasting intervention strategies for various affected populations.