Antimicrobial resistance presents a formidable challenge to contemporary medicine, necessitating innovative therapeutic solutions. Azo dyes and their metal complexes have emerged as promising candidates due to their notable antimicrobial properties. This review comprehensively examines the synthesis and application of azo dyes and metal complexes for emerging antimicrobial therapies. Through various synthetic strategies and metallation, the chemical structure of azo derivatives allows for modifications that enhance their antimicrobial efficacy, making them promising candidates for pharmaceutical development against microbial infections. The study provides a comprehensive understanding of the mechanisms of antimicrobial action, including DNA intercalation, enzyme inhibition, membrane disruption, and reactive oxygen species generation. The role of metal ions is particularly significant, enhancing structural stability, reactivity, and the ability to target microbial enzymes effectively. Chelation effects, such as reduced polarity and increased lipophilicity, facilitate the penetration of microbial cell membranes and the disruption of enzyme activity. The review highlights novel azo-metal complexes’ significant antifungal and antibacterial activities, particularly their efficacy against pathogens such as Mycobacterium tuberculosis. The importance of structure-activity relationships is detailed, showing how specific functional groups and metal ions influence antimicrobial efficacy. Additionally, their potential sensing ability to detect and identify microorganisms highlights the multifaceted role of azo dye derivatives in infection management.