Control of postoperative inflammation is a critical component of clinical management following phacoemulsification surgery, and topical corticosteroids remain the standard of care for this purpose; however, the comparative efficacy and safety profiles of fluorometholone (FML) versus dexamethasone (DEX) remain incompletely characterized due to the limited number of direct head-to-head clinical trials available in the literature. This systematic review screened studies comparing topical FML 0.1% against DEX 0.1% for the management of postoperative inflammation following phacoemulsification in adult patients without pre-existing ocular inflammatory conditions, with outcomes assessed including anterior chamber cell and flare grading, intraocular pressure (IOP) changes, incidence of cystoid macular edema (CME), and visual acuity, with data systematically extracted from both randomized controlled trials and observational studies. Direct comparative data between the two agents were limited; two independent network meta-analyses consistently ranked DEX as superior to FML for CME prevention, with DEX demonstrating the highest SUCRA probability [3,4], while one RCT reported that FML was associated with early IOP elevation, with 4.98% of patients experiencing a rise of ≥10 mmHg, whereas DEX showed no comparable elevation [1]. A separate meta-analysis comparing standard versus soft steroids demonstrated significantly lower anterior chamber flare with standard steroids (including DEX) at day 7 (SMD 0.26, 95% CI 0.05–0.47), though this difference did not persist at day 28 [5], and pharmacokinetic analyses revealed that FML achieves peak aqueous humour concentrations approximately 130-fold lower than prednisolone and substantially lower than DEX [6], with one study finding no significant difference in aqueous flare between FML and no steroid treatment at all [7]. These findings indicate that DEX demonstrates superior anti-inflammatory efficacy, particularly in preventing CME, likely attributable to its greater intraocular penetration capacity, whereas FML appears to offer a more favourable IOP safety profile across most available studies, although one contradictory trial reported higher IOP spikes associated with FML use, carrying the clinical implication that DEX is more effective for managing intraocular inflammation while FML may be adequate for mild ocular surface inflammation or as a step-down maintenance agent following initial DEX therapy. In conclusion, dexamethasone 0.1% demonstrates greater efficacy than fluorometholone 0.1% in controlling postoperative intraocular inflammation and preventing CME after phacoemulsification, albeit with a potentially elevated IOP risk in susceptible patients, and based on current evidence, fluorometholone should not be employed as first-line monotherapy for intraocular inflammation control following cataract surgery.