One of the main issues in oncology is tumor recurrence following resection, which is responsible for a large number of patient deaths and treatment failures in a variety of malignancies. Despite advancements in adjuvant chemotherapy and radiation, residual disease that remains inside or close to the resection cavity and is difficult for systemic therapies to eradicate is the cause of further local recurrence. Hydrogel-nanoparticle (HNP) composites are a new class of therapeutic platforms that emerged from the recent convergence of biomaterial science and nanomedicine. Their specific goals are to fill the surgical gap, provide long-term localized drug release, and energetically remodel the post-surgical tumor microenvironment (TME). This paper includes the biological foundations of localized post-surgical therapy, important physicochemical considerations of the hydrogel matrix and nanoparticle carrier design, and a compilation of mechanistic and preclinical evidence for HNP hybrid platforms. Immunomodulatory strategies, stimuli-responsive release mechanism engineering, and novel techniques, including combination immunotherapy and 3D-printed customized scaffolds, are all given special attention. Examples of translational challenges are also addressed, such as manufacturing repeatability, biocompatibility, and regulatory classification. When considered collectively, the data demonstrate that HNP platforms are a convincing, practically feasible approach to reducing post-surgical recurrence rates and enhancing patient outcomes.