Beyond Panama south there is no reliable road. Impassible dangerous any time the roads turn to dirt track and only a few 4wd vehicles make the Beyond Panama south there is passage through the Darien passage through the Darien Gap. Otherwise air or boat is Gap. Otherwise air or boat is the only way to reach south America from Panama.
See article for boat info
With Tica Bus service through Central America you stay on the same bus if you choose and cross the borders.  This can make the trip safer and simpler.
The
Tica Bus line runs a total of 38 air-conditioned buses
Cross Border Bus, Central America, Tica Bus Service
Central America Bus Travel,
The Tica Bus, cross- border buses with Luxury Seating at a Backpackers Price
Bus Central America: Cross borders on the same bus with the Tica Bus

For independent travelers through Southern Mexico to Central America as far south as Panama City there is a bus option that takes some of the anxiety out of crossing the borders and finding the next bus. This system is called the Tica bus for short and stands for Tansportes Internacionales Centroamericanos:

The 2014 ticket price for a trip from Tapachula in Chiapas Mexico to Panama City Panama in Central America is $356. USD round trip, paid in US Dollars, travelers checks, or the currency of the country only, no checks or credit cards accepted.

Make reservation
via email and pay when arriving at the terminal.

The
Cross Border trip leaves Mexico and goes through Guatemala to El Salvador where it stops for the night. The bus then goes to Managua and stops for the overnight. The bus then makes a day and overnight trip to Panama.
Schedule for trip South from Tapachula in Chiapas, Mexico.
Leave Tapachula at 7:00 am, arrive at Guatemala at 12:00 noon.

Leave Guatemala at 1:00 p.m,,arrive at El Salvador approximately at 5:00 p.m.

Leave El Salvador at 5:00 a.m,,arrive at Nicaragua approximately
at 5:00 p.m.

Leave Nicaragua at 6:00 a.m,,and 12:00 noon, arrive at Costa Rica approximately at 4:00 p.m, 5:00 p.m. and 9:00 p.m.

Leave Costa Rica at 10:00 p.m. on the same day and arrive at Panama at 4 in the afternoon the following day.
Passengers can stop for extended stays in the terminal cities, the ticket is still honored, they must however make a reservation and reserve a seat to continue. Passengers pay additional for their hostel or hotel, and food. Other expenses that are the passenger’s responsibility would be the visa and each country’s customs charge which averages $10

Tica runs a total of 38 air-conditioned, 54-passenger buses that have reclining seats, restrooms, window curtains, TV and video.
Tica Buses  serve Central America between Mexico and Panama. Buses have reclining seats, lavatory, window curtains, TV and video.
For the cross-border Tica bus, the  trip starts in Tapachula, Chiapas Mexico with service to Panama City, Panama in Central America
Cross Border Bus to Central America via the Tica for 2014has a ticket price from Tapachula, Chiapas Mexico to Panama City Panama of $356. USD Round trip.
ADO Bus Sells tickets for Tica Bus to Guatemala In Oaxaca City first class bus station  
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Tica Bus Fares 2014

Tapachula, Chiapas, Mexico to  Guatemala  Economy One Way $19.00   Round trip $38.00

  • Tapachula, Chiapas, Mexico to El Salvador:  Economy  $37.00 One Way,    $74.00  Round Trip
  • Tapachula to Nicaragua  Econ.  $86.00,   $172.00 RT     
  • Tapachula to Costa Rica Econ. $135.00    $270.00  RT    
  • Tapachula to Panama      Econ  $176.00  $$352 USD  RT     
  • Tapachula  to Tegucigalpa, Honduras     Economy Only   $52.00     $104.00 RT
Fares are approximate as of July 2014 and do change without notice
Buy Tica Busd tickets to Guatemala through OCC in Tapachula or online via email.