Chronic myeloid leukemia (CML) treatment in low- and middle-income countries faces significant financial and logistical constraints. In scenarios where second-line tyrosine kinase inhibitors (TKIs) are unavailable or unaffordable, dose escalation of imatinib provides an alternative. This study evaluates the efficacy, safety, and progression-free survival (PFS) outcomes of dose escalation of imatinib in CML patients who experienced suboptimal response or progression on standard doses. A retrospective analysis of 123 CML patients treated at an Indian university teaching hospital from 2013 to 2016 was conducted. Patients who showed progression on a 400 mg dose of imatinib were escalated to 600 mg, and further to 800 mg if required. Demographic data, progression, and toxicity were analyzed. Out of 123 patients, 78 (63.4%) showed a complete hematologic response after dose escalation. The median PFS was 48 months, with a three-year PFS rate of 67%. Notable toxicities included Grade 3/4 neutropenia in 15% and gastrointestinal disturbances in 12%. Comparatively, studies suggest that switching to a second-line TKI in similar settings results in a higher PFS; however, our findings underscore that dose escalation of imatinib remains a viable alternative when financial constraints limit access to second-line therapies. In resource-constrained settings, dose escalation of imatinib can be an effective strategy for managing CML patients who progress on standard doses.