Vitamin D is a fat soluble secosteroid that is primarily synthesized in the skin upon exposure to Ultraviolet B (UVB) sun rays. Vitamin D is essential for the growth and development of bones and helps in reducing inflammation by strengthening muscles and the immune system. Despite the endless supply of sunlight in the Gulf Cooperation Council (GCC) countries which includes United Arab Emirates, Qatar, Kuwait, Bahrain, Saudi Arabia, and Oman, Vitamin D deficiency in the (GCC) general population at various age groups remains alarmingly high. In parallel runs the increasing prevalence of acute and chronic illnesses including, autoimmune diseases, cancer, type 1 diabetes mellitus, cardiovascular disease and Inflammatory bowel disease in the adult as well as the pediatric population of these countries. The exact association between Vitamin D deficiency and chronic disease conditions remains unclear; however, studies have focused on the mechanism of Vitamin D regulation by assessing the role of the Vitamin D associated genes/proteins such as VDR (Vitamin D receptor), VDBP (Vitamin D Binding protein), CYP27B1 as these are integral parts of the Vitamin D signaling pathway. VDR is known to regulate the expression of more than 200 genes across a wide array of tissues in the human body and may play a role in controlling the Vitamin D levels. Moreover, reduced Vitamin D level and downregulation of VDR have been linked to gut dysbiosis, highlighting an intriguing role for the gut microbiome in the Vitamin D metabolism. However, this role is not fully described yet. In this review, we aim to expand our understanding of the causes of Vitamin D deficiency in the GCC countries and explore the potential relationship between the genetic predisposition, Vitamin D levels, immune system and the gut microbiome composition. Trying to unravel this complex interaction may aid in understanding the mechanism by which Vitamin D contributes to various disease conditions and will pave the way toward new therapeutics treatments for Vitamin D deficiency and its associated outcomes.