Take the new highway to Caldera. Make sure you have change to pay the tolls. Drive up to Multiplaza Mall and take the Prospero Fernandez Highway, follow the signs to Jacó. Keep going and, on your left,  you will encounter the Carara national park, stay on that road until you get to Quepos.
Once in Quepos take the road to the Manuel Antonio National Park. At km # 5, on the left hand side, you will find the hotel's reception.

Alternative Road

The trip takes about three hours. When leaving San José take the main highway (Carretera Interamericana) going North towards Puntarenas. The highway will pass the Juan Santa María international airport. Stay on the Interamericana for about 10-15 minutes more, until you see an exit for a town called Atenas. Take this exit and keep going; you will see signs for Jacó and Quepos, as you go through the towns of Atenas, San Mateo, Orotina, and Tarcoles (YOU MUST GO THROUGH THESE TOWNS). You wiil pass over the Tarcoles River, and keep going until you get to Jacó. Stay on the main road, until you get to Quepos. Once in Quepos take the road to the Manuel Antonio National Park. At km # 5, on the left hand side, you will find the hotel's reception.