Due to an environment that promotes gravitational interactions and ram pressure stripping, galaxies within clusters are particularly likely to present unusual interstellar medium (ISM) properties. NGC 4654 is a Virgo cluster galaxy seen almost face-on, which undergoes nearly edge-on gas ram pressure stripping and a fly-by gravitational interaction with another massive galaxy, NGC 4639. NGC 4654 shows a strongly compressed gas region near the outer edge of the optical disk, with Hi surface densities (high Hi surface density region) significantly exceeding the canonical value of 10-15 M pc −2. New IRAM 30m HERA CO(2-1) data of NGC 4654 are used to study the physical conditions of the ISM and its ability to form stars in the region where gas compression occurs. The CO-to-H 2 conversion factor was estimated by (i) simultaneously solving for the conversion factor and the dust-togas ratio by assuming that the latter is approximately constant on giant molecular cloud scales and (ii) by assuming that the dust-togas ratio is proportional to the metallicity. The CO-to-H 2 conversion factor was found to be one to two times the Galactic value. Based on the comparison with a region of similar properties in NGC 4501, we favor the higher value. We observe a significant decrease in the ratio between the molecular fraction and the total ISM pressure in the high Hi surface density region. The gas in this region is selfgravitating, with a Toomre parameter below the critical value of Q = 1. However, the star-formation efficiency (SFE H 2 = Σ SFR /Σ H 2) is 1.5 to 2 times higher, depending on the assumed conversion factor, in the high Hi surface density region than in the rest of the disk. Analytical models were used to reproduce radial profiles of the SFR and the atomic and molecular surface densities to better understand which physical properties are mandatory to maintain such high Hi surface density regions. We conclude that a Toomre parameter of Q ∼ 0.8 combined with an increase in the velocity dispersion of ∆v disp ∼ 5 km s −1 are necessary conditions to simultaneously reproduce the gas surface densities and the SFR. A dynamical model that takes into account both gravitational interactions and ram pressure stripping was used to reproduce the gas distribution of NGC 4654. While the ISM properties are well reproduced in the whole disk, we find that the model SFR is significantly underestimated in the high Hi surface density region due to the absence of gas cooling and stellar feedback. The comparison between the velocity dispersion given by the moment 2 map and the intrinsic 3D velocity dispersion from the model were used to discriminate between regions of broader linewidths caused by a real increase in the velocity dispersion and those caused by an unresolved velocity gradient only. We found that the 5 km s −1 increase in the intrinsic velocity dispersion predicted by the model is compatible with the observed velocity dispersion measured in the high Hi surface density region. During a period of gas compression through external in...