The plant kingdom offers a wealth of molecules with potential efficacy against various human, animal, and plant crop infections and illnesses. Cannabis sativa L. has garnered significant attention in recent decades within the scientific community due to its broad biological activity. Key bioactive compounds such as cannabinoids and phenolic compounds have been isolated from this plant, driving its bioactivity. Numerous studies have highlighted the impact of different agronomic practices, particularly fertilization, on the phytochemical composition, notably altering the percentage of various chemical groups. This review aims to present updated fertilization recommendations, crop requirements, and their implications for the chemical composition of C. sativa plants, along with major biological properties documented in the literature over the past five years. Various databases were utilized to summarize information on fertilization and crop requirements, chemical composition, bioassays employed, natural products (extracts or isolated compounds), and bioactivity results. Through this review, it is evident that C. sativa holds promise as a source of novel molecules for treating diverse human diseases. Nonetheless, careful consideration of agronomic practices is essential to optimize chemical composition and maximize therapeutic potential.