Background: Involuntary weight loss may occur during systemic anti-cancer therapy (SACT), causing treatment disruption and poorer prognoses. There remain gaps in clinical awareness as to which patients may benefit from nutritional interventions that aim to prevent unintended weight loss during SACT. We utilised England’s population-level cancer registry data, conducting a pan-cancer assessment of patient weight loss during SACT. We aimed to identify cancers with weight loss-associated treatment modifications, potential beneficiaries of nutritional intervention. Methods: This cross-sectional study used England’s Cancer Analysis System database, including SACT-treated adults with one tumour and ⩾2 weight recordings between 2014 and 2018. Binary weight loss (threshold: 2.5%) was derived from patients’ most negative weight change from first SACT weight recording. The Martin et al. body mass index-adjusted weight loss grading system (BMI-WLG) was assigned. We describe binary weight loss, BMI-WLG and treatment modification status by cancer. Multivariate logistic regression models of weight loss (binary and BMI-WLG) and a composite outcome of patient treatment-modification status by cancer were produced. Results: Our study population contained 200,536 patients across 18 cancers; 28% experienced binary weight loss during SACT. Weight loss patients were more likely to have multiple types of treatment modifications recorded across all cancers. Regression analyses included 86,991 patients. Binary weight loss was associated ( p