<p>The century-old vision of a “magic bullet” in oncology is being realized through the paradigm of precision theranostics, which formally integrates targeted delivery, cytotoxic action, and non-invasive imaging into a unified clinical feedback loop. This review synthesizes the cutting-edge convergence of three interdependent pillars: antibody-drug conjugates (ADCs), which act as Trojan horses delivering potent cytotoxic payloads; radioimmunotherapy (RIT), which harnesses the power of radionuclides for crossfire-mediated cytotoxicity; and advanced molecular imaging, which orchestrates patient stratification and early response assessment. We dissect the mechanistic innovations in ADC design, the renaissance of RIT with novel isotopes and targets, and the pivotal role of immuno-PET in enabling an “image-to-treat” paradigm. Furthermore, we explore the synergistic frontier of rationally combining ADCs and RIT to overcome resistance through multi-mechanistic attacks, leveraging radiation for payload activation, and priming the tumor microenvironment. Despite challenges in toxicity management, radiopharmaceutical supply, and regulatory frameworks, the integration of these modalities, guided by artificial intelligence and functional imaging, heralds a new era of dynamic, personalized, and adaptive cancer therapy. This integrative approach promises to convert tumor heterogeneity from a fundamental obstacle into a targetable vulnerability; however, this promise must be tempered by clinical examples in which heterogeneity undermined otherwise promising targeted approaches (for example, subclonal RAS mutations limiting benefit from anti-EGFR monoclonal antibodies in colorectal cancer). We therefore emphasize lesion-level imaging and adaptive, imaging-guided sequencing as realistic, evidence-based mechanisms by which theranostics can reduce the impact of intratumoral heterogeneity and improve the chance of durable benefit.</p> Graphical Abstract <p></p>