The convergence of targeted imaging agents with intraoperative guidance systems is reshaping oncologic surgery to enable precision tumor resection and reduce residual disease. We examine the evolving role and integration of cancer theranostics with advanced image-guided intraoperative imaging to improve surgical precision and the targeted removal of diseased tissue while sparing normal vital structures. Molecularly engineered probes, for instance, the EGFR-targeted antibody conjugated with IRDye800CW and the folate receptor alpha-targeting agent, OTL38, delineate tumor margins with high sensitivity and specificity, and investigational tumor-targeting probes that combine preoperative PET imaging with real-time surgical navigation maximize tumor detection and removal for improving patient outcomes. These approaches exploit near-infrared (NIR) optical windows to overcome limitations at visible wavelengths, including shallow light penetration and autofluorescence, and enhance sensitivity and spatial resolution. In parallel, advances in imaging hardware and software have led to new artificial intelligence (AI)-powered surgical navigation devices, multispectral cameras, gamma probes, and Cerenkov luminescence systems that complement the molecular precision of these probes by offering enhanced depth detection and/or dynamic visualization. The integration of AI and augmented reality further refines image registration and quantitative analysis, ensuring that intraoperative feedback is accurate and actionable. The synthesis of molecular targeting and state-of-the-art imaging addresses the critical clinical need of achieving complete tumor resection, a key determinant of patient prognosis and recurrence. Recent Phase 2 and Phase 3 trials underscore the translational potential of these theranostic approaches, which are rapidly advancing toward routine practice. By enabling personalized and adaptive surgical strategies, the integration of cancer theranostics and intraoperative imaging represents a vital step forward in precision oncology, promising significant improvements in long-term patient outcomes.