Cancer dormancy is a clinical phenomenon commonly found in various types of cancer, and is recently thought to offer a potential therapeutic target. Since, in general, only actively replicating cells are targeted by most cancer therapies, these dormant cells can still persist even after exceedingly long treatment durations and are responsible for chronic residual diseases in patients. These disseminated, dormant cells can be reactivated to become proliferating again in the wake of comprised immunity or changes in microenvironment factors. Relapse can thus occur after long periods of remission that range from years to decades. Such a pause in disease progression gives rise to the problem of dormancy, an uncertainty one must address in order to improve health outcomes of patients. To address this issue, we work on a unifying mathematical framework, explicitly taking into account the role of dormancy and reactivation in disease relapses. We derive analytical results to address questions of clinical interest and importance, including ascertaining the timing of when metastatic (secondary) tumors become clinically observable and, if so, how many of them are observable. Moreover, we hypothetically study ‘anti-dormancy’ therapy aimed at eliminating the reservoir of disseminated dormant tumor cells. We calculate the minimum duration and efficacy of anti-dormancy treatment that is required to substantially prolong the life expectancy of cancer patients. Our mathematical framework can be used to assess the efficacy of different postoperative targeted treatments, such as targeting either dormant cells or active metastatic cells or targeting both at the same time. This work, although probed in the specific context of cancer, can be readily extended to predict outcomes of treatments targeted at bacterial persistence and HIV latency.