The global rise of multidrug-resistant (MDR) infections, driven by increasing antimicrobial resistance (AMR), represents one of the most pressing challenges for public health. AMR leads to treatment failures, increased morbidity and mortality, higher healthcare costs, and prolonged recovery times, highlighting the urgent need for effective and safe alternative therapies. This concern is exacerbated by the declining rate of new drug approvals in recent decades, particularly in the field of antimicrobials (ATMs). According to the World Health Organization, AMR caused by bacteria, viruses, and fungi is a critical threat that demands innovative strategies, including the development of advanced antimicrobial agents. Nanotechnology has emerged as a disruptive and promising approach to tackle AMR. Due to their nanoscale dimensions, nanomaterials and nanoparticles exhibit unique physicochemical properties—such as high surface-to-volume ratios, tunable surface functionalities, and enhanced reactivity—making them ideal candidates for next-generation antimicrobial applications. Recent advances have led to the design of functionalized nanomaterials that act as antibiotic carriers, possess intrinsic antimicrobial properties (e.g., metal-based nanoparticles), or combine both mechanisms. These engineered nanomaterials have demonstrated enhanced drug delivery, increased efficacy, and strong anti-biofilm activity, thereby helping to reduce the emergence of resistance, a major limitation of conventional antibiotics. In addition, nanoparticles have shown the capacity to penetrate microbial biofilm matrices, offering a potent alternative for treating persistent infections. This chapter explores the concept of “nanotechtonics”—the integration of advanced materials science and microbiology—as a novel framework for combating MDR pathogens. It provides an overview of the mechanisms behind AMR, the design, and the mode of action of various nanoparticles. It compares the effectiveness of conventional antimicrobials versus nano-enabled antimicrobials against both planktonic and biofilm-associated microorganisms. Despite the promising potential of nanotechnology, several challenges remain, including ensuring biocompatibility, addressing environmental impacts, and navigating complex regulatory landscapes. Nevertheless, the transformative potential of nanotechtonics underscores its critical role in the fight against AMR. Continued investment in research, development, and safety evaluation will be essential to translate these technologies into clinical practice.