Durum wheat is one of the most important food sources in the world, playing a key role in human nutrition, as well as in the economy of the different countries in which its production areas are concentrated. Its grain also represents a staple and highly versatile ingredient in the development of health foods. Nonetheless, the aspects determining durum wheat’s health quality and their interactions are many, complex, and not entirely known. Therefore, the present systematic literature review aims at advancing the understanding of the relationships among nutritional, health, and technological properties of durum wheat grain, semolina, and pasta, by evaluating the factors that, either positively or negatively, can affect the quality of the products. Scopus, Science Direct, and Web of Science databases were systematically searched utilising sets of keywords following the PRISMA guidelines, and the relevant results of the definitive 154 eligible studies were presented and discussed. Thus, the review identified the most promising strategies to improve durum wheat quality and highlighted the importance of adopting multidisciplinary approaches for such purposes.