The accelerating emergence of multidrug-resistant bacteria represents a critical global health challenge and underscores the urgent need for new antibacterial agents capable of treating infections that are increasingly unresponsive to existing therapies. Antibiotic resistance, driven largely by misuse, overuse, and unregulated access, has prompted the World Health Organization (WHO) to identify 12 priority bacterial families for which treatment options are severely limited, raising concern over a potential post-antibiotic era. Addressing this challenge requires the discovery of antibacterial candidates featuring novel chemical scaffolds and alternative mechanisms of action. Fused imidazonaphthyridine frameworks have attracted increasing attention in medicinal and synthetic organic chemistry owing to their diverse biological activities, including anti-inflammatory, antiviral, and anti-hepatitis effects. Based on this pharmacological potential, the present study reports the rational design and synthesis of a series of novel imidazonaphthyridine derivatives as prospective antibacterial agents. All compounds were fully characterized using standard spectroscopic techniques and subsequently evaluated in vitro against selected clinically relevant Gram-positive and Gram-negative bacterial strains. It is anticipated that the synthesized derivatives will exhibit measurable antibacterial activity within the tested concentration range of 2–256 µg/mL. By expanding the accessible chemical space of antibacterial scaffolds, this work aims to contribute to the development of alternative therapeutic strategy and to provide preliminary structure–activity relationship insights that may inform future antibacterial drug discovery efforts.