The railway had to run for long distances next to the sea and follow the twists of the coast to minimise the number and length of tunnels.

Furthermore, since materials had to be transported by sea because long stretches of coastline were inaccessible by land, work was delayed by violent storms.

[10] Operations are managed and controlled by the Sistema di Comando e Controllo ("command and control system"—SCC, an Italian version of centralized traffic control) of the Rete Ferroviaria Italiana, the subsidiary of the Ferrovie dello Stato group that is responsible for the management of the infrastructure, which supervises the rail traffic from the operations centre in Pisa for the section that runs from Civitavecchia to Sestri Levante (about 420 km) and from the operations centre of Genova Teglia for the section from Sestri Levante to the node of Genoa.

The landscape, characterised by the passage between villas, coast and cliffs, remains almost unchanged along the whole of the Golfo Paradiso as far as Camogli-San Fruttuoso.

After crossing the promontory of Portofino, the line follows the Gulf of Tigullio, serving the tourist resorts from Santa Margherita Ligure to Riva Trigoso.

The line then crosses the localities from Moneglia to Monterosso, which is at the beginning of the Cinque Terre section, noted for its long tunnels and sudden glimpses of the Ligurian Sea, picturesque villages and sheer cliffs.

In Tuscany, the line runs through the provinces of Massa and Carrara and Lucca, remaining almost at the centre of the plain formed over the centuries between the chain of the Apuan Alps and the coast.

During the construction of a building that was to have housed a new electronic control centre, which was subsequently moved to another location, the remains of an ancient Roman port were found.

A shed that housed the royal train when the Italian king resided at the San Rossore estate still exists to the north of the station.

In Genoa, remains of a portion of the bridge over the Vernazza river at Sturla and a tunnel mouth next to the Via Gianelli at Quinto al Mare are still visible.

Since its opening, the Genoa–Pisa railway carried substantial traffic as it is a main line connecting Liguria and Piedmont, with Tuscany, Lombardy and southern Italy.

These services proved to be particularly valuable both in the city of Genoa, thanks to the presence of numerous toll booths and stops, and, in the Cinque Terre, due to the lack of roads.