Currently, microbial infections have posed an arduous challenge to global public health, whereas the rise of antibiotic resistance is rendering traditional antibiotic therapies futile, prompting the development of new antimicrobial technologies. Photoactive nanomaterials have thus garnered a thriving interest for disinfection owing to their superior antibacterial efficaciousness, favorable biosafety, and rapidness and spatiotemporal precision in excreting bactericidal actions. The review summarizes recent advances and emerging trends in the design, nanoengineering, and bioapplications of photoactive antimicrobials. It commences by elaborating fundamental theories on bacterial resistance, and antibacterial mechanisms of nanomaterials and phototherapy. Subsequently, the regulation of the antibacterial effectiveness of photoactive nanomaterials is comprehensively discussed, centering on criteria and strategies for tuning photoabsorption spectra, photothermal conversion, and photocatalytic efficiency, alongside tactics for enabling synergistic therapies. This is followed by comparative analyses of techniques and modalities for synthesizing and engineering photoactive nanomaterials with diverse structures, forms, and functionalities. Thereafter, the state‐of‐the‐art applications of phototherapies across various medical sectors are portrayed, and key challenges and opportunities are finally discussed to spur future innovations and translation. This review is envisaged to provide useful guidance for devising and developing nanomaterials‐based photoresponsive antimicrobials with application‐specific materials properties and biological functions.