Nutraceuticals are bioactive compounds or functional foods consumed to sustain nutrition and support disease prevention. Derived from nutrition and pharmaceuticals, the concept merges food science with therapeutic potential. Synergism in nutraceutical formulations arises when two or more bioactive agents interact to produce enhanced pharmacological or physiological outcomes that surpass the sum of their individual effects. This principle addresses key challenges of monotherapy: poor bioavailability, limited target specificity, and rapid metabolic degradation by enabling multicomponent, mechanistically complementary formulations. Recent innovations such as nano-encapsulation and codelivery systems further enhance absorption, stability, and efficacy of synergistic blends. This chapter provides a comprehensive overview of molecular and formulation-based synergism in nutraceuticals, focusing on mechanistic interactions, formulation challenges, and future directions toward supernutraceuticals that integrate advanced bioengineering and traditional dietary wisdom.