OBJECTIVE: To noninvasively monitor cardiac functional changes throughout chemotherapy in colorectal cancer patients using pressure-strain analysis, validate their predictive value for early detection of subclinical cardiac dysfunction. METHODS: This retrospective observational study included colorectal cancer patients receiving FOLFOX/CAPEOX chemotherapy. Myocardial work parameters-including global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE)-were serially assessed using noninvasive pressure-strain loop technology at baseline (T0), after the first cycle (T1), mid-therapy (T2), and treatment completion (T3). Its predictive performance was evaluated by analyzing the trends of the aforementioned parameters and using receiver operating characteristic (ROC) curves. RESULTS: Significant cardiac dysfunction emerged as early as the first chemotherapy cycle: GLS decreased by 8.7% (p < 0.001), GWI declined by 6.2% (p < 0.001), GWE reduced by 0.5% (p < 0.001), and GWW markedly increased (p < 0.001). The combined myocardial work model (GWI + GCW + GWE + GWW) predicted subclinical dysfunction with superior AUC (0.875) versus the GLS-only model (AUC = 0.813, p = 0.037). CONCLUSIONS: FOLFOX/CAPEOX chemotherapy induces early myocardial mechanical inefficiency. Myocardial work parameters are sensitive monitoring markers, and their integrated model enhances early detection of subclinical cardiac injury.