Purpose: Post-surgical refractory gastroparesis (PSRG) presents a significant management challenge, with no reliable predictors for the success of gastric peroral endoscopic myotomy (G-POEM). This study aims to evaluate the utility of intra-pyloric botulinum toxin (Botox) injection as a potential predictor for G-POEM success. Methodology: This retrospective study involved 24 patients with PSRG who underwent intra-pyloric Botox injection followed by G-POEM. Demographic data, comorbidities, and baseline Gastroparesis Cardinal Symptom Index (GCSI) scores were recorded. The primary outcome was the correlation between GCSI scores before and after Botox and G-POEM. Secondary outcomes included length of stay (LOS), morbidity, and re-intervention rates. Results: The study demonstrated that patients who showed significant improvement in GCSI scores post-Botox injection had a positive correlation with G-POEM clinical success (positive predictive value of 73.68%). The rate of adverse events was 37.5%, and clinical success, defined as a 1-point decrease in average GCSI scores with a 25% reduction in at least two sub-scores, was achieved in 75% of patients at the 12-month follow-up. Conclusion: Intra-pyloric Botox injection appears to be a reliable predictor of G-POEM success in treating PSRG, especially in patients with a tight pyloric sphincter. The findings support further investigation of Botox as a pre-treatment predictor for G-POEM outcomes.