Cancer-related cognitive impairment is prevalent in metastatic lung cancer survivors. This study aimed to compare the effectiveness of aerobic exercise and Tai Chi on perceived cognitive function and the mediating role of psychoneurological symptoms with perceived cognitive impairment. In a subgroup of a parent randomized clinical trial, participants who reported cognitive impairment underwent a 16-week aerobic exercise (n = 49), Tai Chi (n = 48), and control (n = 54) groups. Measures included perceived cognitive function and psychoneurological symptoms (sleep disturbance, fatigue, anxiety, and depression) assessed at baseline (T0), 16-week (T1), and 1year (T2). Participants in Tai Chi showed significant improvements compared to aerobic exercise and control groups in perceived cognitive function at T1 (AE: between-group difference, 6.52; P < 0.001; CG: 8.34; P < 0.001) and T2 (AE: between-group difference, 3.55; P = 0.05; CG: 5.94; P < 0.001). Sleep disturbance, fatigue, anxiety, and depression at month 12 explained 24%, 31%, 32%, and 24% of the effect of the intervention on cognitive function at month 12, respectively. Only anxiety at month 4 explained 23% of the intervention effect at month 12. Tai Chi demonstrated beneficial effects on cognitive function in advanced lung cancer survivors with perceived cognitive impairment. Improvement in cognitive function was mediated by reducing sleep disturbance, fatigue, anxiety, and depression, highlighting the importance of addressing these symptoms in future interventions to improve cognitive function, with anxiety playing a significant role at an earlier stage. Tai Chi is a potentially safe complementary therapeutic option for managing cognitive impairment in this vulnerable population. ClinicalTrials.gov identifier: NCT04119778; retrospectively registered on 8 October 2019.