Not only are there average daily temperature fluctuations from -80 °C to 20 °C - night to day depending on time of year and latitude to contend with. They can go much lower depending on the season. There is also the cosmic radiation on man and machine, both on the journey and on the surface. The only current solutions are to add mass to a shield or go underground.
Recent research, however, throws up newer problems - the loss of bone density in the astronauts and cardio issues. On a six month trip to the space station they lose an average of 2.1% density in their leg bone, the tibia, and 1.3% reduced bone strength. This is a permanent change even when back on Earth. It will be even worse on Mars where the gravity is only 40% that of Earth. A round trip - touch down and come back - will take about 14 months. A short stay, a few months, makes things worse.
There is also the issue that micro-gravity has on the cardiovascular system. On Earth gravity pulls blood towards our feet to then be pumped back around our bodies. We are built to cope with that. In space we do not have that so blood pools in our upper bodies, which effects blood pressure and vision. Some astronauts might not be able to come back.