INTRODUCTION: Radiation-induced lymphopenia (RIL) has been shown to adversely affect the prognosis of cancer patients undergoing radiotherapy (RT). This model-based meta-analysis investigated the prognostic significance of lymphocyte counts both early and late after RT and examined the dose‒response relationship between post-RT lymphocyte levels and patient survival. METHODS: A literature search of published articles on the effect of RIL on cancer prognosis was conducted using the PubMed and Cochrane databases. A survival model was developed, incorporating absolute lymphocyte count (ALC) thresholds during (1 month after RT initiation, nadir) and 6 months after RT (recovery) as covariates to estimate progression-free survival (PFS) and overall survival (OS). This survival model, with the lymphocyte count cutoff as a covariate, was then used to simulate the benefit of increased PFS and OS in populations without lymphopenia or severe lymphopenia compared to the total population. RESULTS: A total of 35 studies met the inclusion criteria for survival analysis. Our survival model revealed an increase in survival in the subgroup without lymphopenia compared to the total population. The subgroup without lymphopenia 1 month after RT initiation showed a 10.28 % and 3.92 % increase in 24-month PFS and OS, respectively. The subgroup without lymphopenia at 6 months showed a 5.82 % and 2.78 % increase in 24-month PFS and OS, respectively. CONCLUSION: This study highlights the critical role of lymphocyte nadir and recovery following RT in patient prognosis and strengthens the evidence for a causal relationship between RIL and patient outcomes. Expanding the dataset and including randomized controlled trials would provide a more comprehensive understanding of monitoring or knowledge of ALC profiles following RT.