The realm of bioactive compounds has no limits as they are availed naturally, and their presence is in abundance, typically derived from plants, animals, microbiomes, etc. These compounds are primarily categorized based on their natural occurrence and nonnatural occurrence, i.e., either synthetic or semisynthetic. Systems Biology is a potent tool to analyze and predict the genomic, metabolomic, and transcriptomic data of these compounds with a system-wide perspective, leveraging the recent innovations of “omics” and technology, as well as the volume of data generated. A system-oriented approach holds tremendous promise to comprehend the molecular mechanism underlying the significance and intricate features associated with these bioactive compounds that influence the several facets of the healthcare and wellness industry. This revolutionized approach has harnessed the power of the predictive model and network analysis that results in the discovery, validation, and toxicity prediction of novel therapeutics. This chapter focuses on the “Systems Biology” approach to study the potential bioactive ingredients from different sources as nutraceuticals for human welfare. Furthermore, it highlights contemporary developments and examples involving the integration of Precision Medicine and Precision Nutrition for the economical, effective, and prudent use of bioactive compounds fostering sustainability.