Treatment resistance contributes to almost ninety percent of cancer-related deaths. Intratumor heterogeneity and somatic mutability, two key traits of cancer cells, are responsible for this. Overcoming this resistance, a dynamic process, requires strategies based on evolutionary biology. The ‘double bind’ concept, derived from predator-prey dynamics, applies to cancer when initial therapy increases the tumor’s susceptibility to a subsequent treatment. A classic example is radiotherapy, making cancer cells more responsive to immune-based therapies. By appropriately sequencing the treatments and optimizing the timing of administration, the double-blind strategy can help improve patient outcomes. Our goal is to prevent adaptive resistance by exploiting a cellular fate known as therapy-induced senescence (TIS), which is induced by a wide variety of chemotherapies in approximately 31-66% of clinical samples. TIS allows cancer cells to escape the immediate cytotoxic effects of chemotherapies and emerge as more aggressive, therapy-resistant variants by triggering a temporary growth arrest. We speculated that dependence on TIS to develop chemoresistance can be exploited as a double-bind strategy. However, the success of this strategy would rely on eradicating senescent cells within the appropriate therapeutic window, mainly because TIS is a transient event. To confirm our hypothesis, we developed models of adaptive chemoresistance by inducing TIS in triple-negative breast cancer. We identified molecules produced by senescent cells that are likely responsible for the loss of therapeutic sensitivity and used these to select appropriate senolytic agents. Because we monitored the reversibility of TIS, we finally administered the senolytics within the optimal therapeutic window to assess whether this strategy could enhance the antitumor activity of the chemotherapy. As expected, the maximum effectiveness of senolytics was achieved when they were administered during the peak of senescent cell accumulation, which occurs during the transient phase of TIS. This confirmed the dynamic vulnerability of cancer cells to senescence-targeting agents and demonstrated the feasibility of exploiting this dependence as a double-bind strategy. Since TIS is a common outcome of many anticancer treatments, this finding can be validated experimentally and modeled mathematically across various cancer types and a broad range of senotherapeutics. This approach could serve as a valuable preventative strategy against the development of adaptive resistance in clinical settings.