Past Magallanes Interchange, the highway features 5 lanes, with 1 lane designated as motorcycle lanes until it comes near Nichols Interchange, where the toll road starts.
Osmeña Highway becomes a toll road past the Sales Interchange, with motorcycles below 400cc prohibited to use the tolled expressway.
Osmeña Highway starts at the traffic light with Quirino Avenue.
South Luzon Expressway soon enters Biñan, passing near Southwoods, Barangay San Francisco (Halang), and Splash Island, before entering Carmona, Cavite.
It passes through Carmona in about one kilometer, with an exit to serve the town proper, before re-entering Biñan at Santo Tomas Bridge.
The ACTEx name refers to the segment of SLEX from Alabang Exit in Muntinlupa City up to Santo Tomas Exit in Santo Tomas, Batangas.
South Luzon Tollway/ACTEX start past Filinvest Exit (Exit 23), with 2 to 4 lanes per direction and mostly paralleling the four-lane Maharlika Highway (National Highway, National Road or officially Manila South Road/MSR) over Muntinlupa and northwestern Laguna.
The road slightly curves over barangays Bayanan and Putatan on Muntinlupa.
The expressway's first service area, Tollway Plaza, having a Shell gas station and several restaurants such as Jollibee, KFC, Greenwich, Burger King, and others, is also located on this segment.
South Luzon Expressway climbs over the Maharlika Highway (National Road or Manila South Road) through the Alabang Viaduct, before it descends and becomes the Alabang-Calamba-Santo Tomas Expressway (ACTEx) or South Luzon Tollway (SLT).
Due to increasing vehicles congesting on the SLEX within Metro Manila, the Metro Manila Skyway was constructed as a direct, non-stop route from Alabang–Zapote Road in Muntinlupa to Gil Puyat Avenue in Makati, bypassing many of the interchanges of the SLEX, such as those with C-5 Road near Fort Bonifacio and EDSA. Rizal Highway segment runs through the province of Laguna, as well as a segment of Carmona at Cavite province before continuing back to Laguna from Biñan towards the exit at Calamba through the Maharlika Highway.
Osmeña Highway crosses over Arnaiz Avenue, and soon crosses over EDSA at the Magallanes Interchange.