Poly(3,:poly(styrenesulfonate) (PEDOT:PSS) is a frequently used hole transport layer (HTL) that often constrains the stability and efficiency of inverted perovskite solar cells (PSCs) because of its hydrophilic properties. In the study, a hydrophobic fluorinated derivative (PM6) was employed as an interfacial modifier for the PEDOT:PSS layer. Modification with PM6 improved the hydrophobicity and work function (WF) of the PEDOT:PSS and mitigated the formation of charge recombination centers (Pb 0 ) on the perovskite surface. The improvement reduced energy losses at the interface by facilitating hole extraction and transport across the PEDOT:PSS/perovskite interface. The PSCs incorporating PM6-modified PEDOT:PSS demonstrated a power conversion efficiency (PCE) of 19.46%, superior to the 18.11% PCE observed for cells utilizing the unmodified PEDOT:PSS. Moreover, the PSCs were subjected to temperature conditions (25 °C) and 15% relative humidity for a period of 360 h. The PM6-modified PEDOT:PSS device maintained 89.75% of its initial PCE. In contrast, the PCE of the pristine device had dropped to 75.06% of its initial PCE. Thus, the PM6-based modification of the PEDOT:PSS/perovskite interface emerges as a viable strategy to bolster the performance and reliability of inverted PSCs.