With the Panamericana following the coastline all the way to Chile, Southern Peru is prime territory to explore by road. Bus travel is easy and inexpensive. Larger companies such as Soyus serve all major towns. Minivans called combis, and share taxis, shuttle between smaller towns and usually depart from the Plaza de Armas.
By Bus: Numerous companies work the route from Lima to Arequipa. Always take the best service you can afford—aside from the comfort issue, cheaper carriers have less stringent safety standards and the section of highway between Pisco and Tacna is notorious for robbery, especially on overnight services. Cruz del Sur provides the most reliable service. Ormeños has the most departures from Ica, although the quality of their vehicles and onboard service is notoriously patchy.
By Car The Pan-American Highway runs the length of southern Peru, some of it along the coast, some through desert, and some over plateaus and mountains. It's paved and in good condition, but have fully equipped first-aid and repair kits packed. Besides breakdowns, hazards include potholes, rock slides, sandstorms, and heat. You'll find many service stations along this route, most of which have clean bathrooms and convenience stores. Off the highway conditions are less predictable. Roads may be poor in the eastern highlands and around the Paracas Reserve. Four-wheel-drive vehicles are recommended for all driving except within major cities.
Your only real options to rent a car are in Lima or Arequipa.