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Primary prophylaxis with a long-acting granulocyte colony-stimulating factor (G-CSF), such as pegfilgrastim, is recommended when the overall risk of febrile neutropenia (FN) is ≥20% or when patient-specific risk factors (e.g., advanced age, comorbidities like diabetes, poor performance status, prior FN) elevate risk to a clinically meaningful threshold. Administering pegfilgrastim at least 24 hours after cytotoxic chemotherapy supports neutrophil recovery during the expected nadir without antagonizing cytotoxic effect. Waiting for ANC decline (Option C) fails to prevent first-cycle FN, which is associated with dose reductions, delays, hospitalizations, and mortality. Routine antibiotic prophylaxis (Option A) is not indicated for most solid-tumor regimens and carries risks of resistance and C. difficile. Deferring G-CSF until after an FN event (Option D) ignores clear indications for primary prophylaxis. APRNs should educate patients on FN symptoms, reinforce the importance of prompt reporting, and coordinate supportive pathways including vaccination, growth factor timing, and dose intensity preservation when clinically appropriate.