Background: This study aimed to evaluate mydriasis stability during cataract surgery in patients with systemic comorbidities such as diabetes mellitus (DM) and pseudoexfoliation syndrome (PXF) after a standardised combination of intracameral mydriatics and anaesthetic (SCIMA). Stable mydriasis is crucial for safe and effective phacoemulsification. Methods: Patients were included if they achieved pupil dilation ≥6.0 mm during the qualifying visit. A total of 103 patients were enrolled, divided into three groups: cataract with diabetes (C + DM group, n = 35), cataract with PXF (C + PXF group, n = 32), and cataract without those comorbidities (C group, n = 36). SCIMA was administered, and pupil diameters were measured at key surgical stages. Stability was defined as a pupil diameter of ≥6.0 mm without additional pharmacological intervention and no significant change in its diameter (≥3.0 mm). Results: Stable mydriasis was achieved in 90.3% of patients: 97.1% in the C + DM group, 90.6% in the C + PXF group, and 83.3% in the C group, with no statistically significant differences (p = 0.14). Conclusions: SCIMA effectively maintains mydriasis stability during cataract surgery, even in patients with systemic comorbidities, ensuring greater surgical safety.