The first major hurdle a Nurse Practitioner would need to overcome is regulatory paperwork. In Florida, Nurse Practitioners can set up private practices and treat patients. Some of the credential required may change in 2015 and require some additional forms of compliance.
On a practical level, one challenge is that many potential patients might still have the prejudice that a nurse is somehow inferior to a doctor. Thus a major marketing challenge is to educate patients concerning the expertise of Nurse Practitioners in precisely the sort of general and family care that is needed in a front line health care provider. You need to communicate to patients that he best cancer specialist or cardiologist in the world may not be a skilled or experienced as a nurse practitioner in dealing with the kid who has just stumbled into a patch of poison ivy, gotten badly sunburned, or eaten a cat toy, and discuss your role in referrals where needed.
The next major challenge is on the business level. Setting up a practice requires handling insurance claims, dealing with government paperwork, dealing with budgets and cash flows, etc. In Florida, Jeb Bush dramatically cut insurance benefits for all state employees, and that has effected the level of reimbursement medical practitioners get from insurance companies and public health programs; making enough money to cover your expenses may be a challenge.