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Objectives This study aims to assess whether single-agent pharmacotherapy directed at the patient-prioritised, highest-scoring PERSONS symptom (target symptom) produces concurrent improvements in both the target symptom and overall symptom burden in advanced-cancer patients.Methods Consecutive adults receiving palliative care specialist between April 2023 and February 2024 were enrolled if ≥1 PERSONS item scored ≥ 7/10. At baseline (T 0), clinicians identified the target symptom and initiated one guideline-concordant drug for its control. Follow-up (T1) occurred after 14 days (median). Outcomes were change in target-symptom severity and change in total PERSONS score. Paired t-tests compared T0 and T1; Pearson’s r examined correlations.Results 81 patients (median age 71years; 55.6% female; 81.5% metastatic disease) completed both assessments. Target-symptom severity fell from 7.63 ± 1.02 to 3.78 ± 1.35 (mean reduction 3.85 points; 95% CI 3.45 to 4.25; p<0.0001). The total PERSONS score decreased from 21.94 ± 4.56 to 13.46 ± 5.12 (mean reduction 8.48 points; 95% CI 7.54 to 9.42; p<0.0001). Target-symptom severity correlated moderately with non-target PERSONS score at T 0 (r = 0.55) and strongly at T1 (r = 0.65; both p<0.0001). Pain was the predominant target symptom (45.7 %).Conclusions Focusing on a single, evidence-based drug on the patient-defined dominant symptom halved target-symptom intensity and reduced global symptom burden by 39% within 2 weeks. These findings support a pragmatic ‘less-is-more’ paradigm that may minimise polypharmacy while delivering broad symptomatic benefit in advanced cancer.