<p>Radioligand theranostics has emerged as a central pillar of precision oncology by integrating targeted molecular imaging and radionuclide therapy within a single molecular platform. Advances in peptide and small-molecule engineering, bifunctional chelators, and radionuclide production have accelerated clinical translation across diverse solid tumors. This review synthesizes recent innovations in radioligand design, emphasizing the mechanistic transition from agonist- to antagonist-based GPCR targeting and the rise of prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP) platforms. Key radiochemistry strategies including direct labeling, chelator-assisted coordination, click chemistry, and kit-based formulations are comparatively evaluated with respect to radiochemical efficiency, pharmacokinetics, and toxicity modulation. Integration of cleavable linkers, next-generation chelators, and hybrid <i>β</i>/<i>α</i> radionuclides (¹⁷⁷Lu, ⁹⁰Y, ²¹²Pb, ²²⁵Ac) has enhanced the therapeutic index while reducing renal and hematologic toxicity. Comparative evidence across PSMA, FAP, GRPR, B7-H3, and PD-L1 demonstrates durable tumor uptake, favorable biodistribution, and expanding clinical feasibility. Alpha-emitter incorporation further extends therapeutic reach beyond conventional <i>β</i>-emitters. Unlike prior target-specific reviews, this article provides a unified mechanistic synthesis linking target biology, radiochemistry platform selection, and translational feasibility. Priority directions include cleavable-linker engineering, adaptive dosimetry, immunoradiotherapy combinations, industrial radionuclide scalability, and global workforce training to support equitable access. Radioligand theranostics is poised to evolve from a specialized niche into a mainstream modality in precision oncology.</p>