The majority of patients with ovarian cancer relapse within 3 years of first line chemotherapy. Therefore, choosing the most appropriate treatment in the recurrence setting has a fundamental role in defining a patient’s prognosis. Treatment options include systemic and intra-peritoneal chemotherapy, secondary cytoreductive surgery, and stereotactic body radiotherapy. The best therapeutic choice depends on multiple factors and not only on treatment-free interval. For systemic therapy, prior lines therapy, residual toxicities, comorbidities, performance status, and patient preferences should be taken into account. Secondary cytoreductive surgery can be proposed in patients in which complete tumor resectability can be predicted and in those with oligometastatic disease. Stereotactic body radiotherapy represents a valid alternative to surgery for oligometastatic disease with high local control and minimal toxicity. Current evidence has demonstrated an emerging role of BRCA mutational status and molecular profiling in the impacting response to systemic and local treatments. Therefore, these could provide guidance in the treatment decision process and help identify patients who respond better to poly(ADP-ribose) polymerase (PARP)-inhibitors or immunotherapy or to a combined approach with surgery rather than to platinum-based chemotherapy. Current knowledge in this field could help widen therapeutic options, especially for platinum-resistant patients. In this review, we offer an overview of the state of the art regarding the role of chemotherapy, radiotherapy, and surgery in this setting and their implications in clinical practice and in the treatment decision process, so as to provide the best tailored therapy in patients with recurrent ovarian cancer.