Background: Solid tumors remain among the leading causes of global cancer mortality, with limited therapeutic options due to drug resistance, toxicity, and tumor heterogeneity. The convergence of nanomedicine and multi-omics technologies offers a novel strategy for precision oncology, enabling targeted drug delivery, biomarker-guided therapy, and improved monitoring of treatment response. Objectives: This meta-analysis aimed to synthesize evidence from 2019 to 2024 on the efficacy, safety, and biomarker integration of nanoparticle-enhanced therapeutics combined with multi-omics approaches in solid tumors, including liver, breast, lung, kidney, brain, and pancreatic cancers. Methods: A systematic search of PubMed, Scopus, and Web of Science was conducted following PRISMA guidelines. Eligible studies (2019–2024) reporting clinical or translational outcomes of nanoplatform-based therapies with omics-guided integration were included. Data were extracted on study design, sample size, tumor types, nanoparticle platforms, omics biomarkers, efficacy outcomes (response rates, progression-free survival [PFS], overall survival [OS]), and toxicity. Pooled analyses were performed using random-effects models. Results: A total of 62 studies comprising ~8,500 patients were included. Lipid-based (38%), polymeric (27%), inorganic (21%), and bioinspired/hybrid (14%) nanoplatforms were evaluated across multiple solid tumors. Pooled analysis demonstrated an improved overall response rate (ORR: 48% vs. 32%, pConclusions: Nanoparticle-enhanced therapeutics integrated with multi-omics approaches show significant promise in improving survival, reducing toxicity, and enabling biomarker-driven precision oncology in solid tumors. However, translational barriers—including tumor heterogeneity, blood–brain barrier penetration, and manufacturing scalability—must be overcome for widespread adoption. The future lies in AI-integrated, stimuli-responsive, bioinspired nanoplatforms guided by multi-omics data, supported by innovative trial designs to ensure clinical translation and equitable global access.