<p>Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, with therapeutic efficacy often hindered by late-stage diagnosis, chemoresistance, and the immunosuppressive tumor immune microenvironment (TIME). This review systematically evaluates the current clinical landscape and emerging breakthroughs in nanomedicine-based interventions for GC. We discuss how unique pathological features of the GC microenvironment such as hypoxia, acidity, and dense stroma—are leveraged to design “smart” stimuli-responsive nanoplatforms for precise drug delivery. Furthermore, the review highlights innovative strategies for TIME remodeling, including macrophage repolarization, cGAS-STING pathway activation, and the integration of multimodal therapies like chemo-photodynamic and immunotherapy. Beyond therapeutics, we examine the pivotal role of nanotechnology in advancing early diagnosis through ultrasensitive biosensors and multimodal imaging probes. Clinically, the successful application of nanoparticle albumin-bound (nab)-paclitaxel underscores the potential of nanomedicine to enhance safety and efficacy. By integrating artificial intelligence (AI) and machine learning for patient stratification, nanomedicine is poised to reshape precision oncology in GC. This review concludes that while challenges in clinical translation persist, the development of bio-inspired nanoplatforms offers a promising frontier for improving the prognostic outlook of gastric cancer patients.</p>