<p>Lycopene is an important carotenoid in human diet with strong antioxidant power and other bioactive functions. As it is sourced from fruits and vegetables, this phytochemical is bound to interact with food components as it is absorbed and metabolized in the organism. Understanding the nature and implications of such interactions is crucial for the prevention of chronic diseases, accurate dietary recommendations and the development of new functional foods, supplements and nutraceuticals. In this review, we explore and discuss current literature on the synergistic effects derived from the combination of lycopene with food phytochemicals, micronutrients and macronutrients. Here, we have focused on peer-reviewed data of in vitro and in vivo studies that brings insights regarding the biochemical mechanisms and health implications of the synergy resulting from the positive interaction between lycopene and food components. We also added some food for thought regarding future research on the matter and a disclosure about the limitations of the review.</p>