According to the Yerushalmi, Esther phrases her question as “what is this and why is this” to demonstrate that she was asking two questions: a) what was the meaning of weeping and b) what was Mordechai’s justification for rejecting the royal clothes she had sent.
Yosef Lekach writes that Esther’s phraseology likens her to a doctor, who diagnoses both the illness and then figures out the cause. Here, also, “what is this” refers to Mordechai’s seemingly strange behavior, and “why is this” refers to the root cause of his concern.
The Ohel Moshe points out that this verse demonstrates just how a great person deals with any tragedy. In any such situation, the great person will seek the spiritual cause, since the spiritual is the actual, whereas the physical/political/personal causes are but a mere reflection in this impermanent, transient mirror to the spiritual world.
The Midrash (Esther Rabbah 8:4) and the Talmud (Megillah 15a) both relate that Esther’s question to Mordechai of two mentions of the word, “zeh” concerned whether or not the Jews transgressed the laws of Moshe’s tablets, which are similarly described as “m’zeh l’zeh” (“from one side to the other”) (Shemos 32:15). R’ Dovid Feinstein explains that Esther was concerned with Torah at this time because she recognized in the gravity of situation that the only cause could be a failure in the Jews’ commitment to the Torah. Interestingly, the Torah was written “mzeh l’zeh” so that each letter could be seen from either side of the tablets. The reason for this, according to Rabbeinu Bachya’s commentary there, is to symbolize the hidden and revealed Torah. Perhaps we can also say that these are the Written and Oral parts of the Torah.
The Midrash (Esther Rabbah 8:4) writes that Esther’s “zeh” question concerned the Jews’ neglecting the responsibilities to which they committed themselves at the splitting of the sea, regarding which is written “zeh Keili vi’anveihu” (“this is my G-d and I will glorify Him”) (Shemos 15:2). The Beis Halevi there explains that both instances of “zeh” precipitated in Amalek’s attack of the Jews in the desert. In other words, the Jewish peoples’ disregard for Torah study and their lack of trust in H-Shem brought Amalek in the desert – and brought their descendant, Haman, in Persia generations later for the same behaviors.
In his unique manner, the Ben Ish Chai focuses on Esther’s use of the word “ma” (“what”). He points out that the letters immediately preceding the mem and hey of “ma” are lamed and dales and the letters immediately after mem and hey are nun and vuv. Together, these four letters spell out “nolad” (“a new creation”). The Ben Ish Chai therefore notes that Esther wanted to know if the Jews were being punished for the previously-mentioned pseudo-idolatry in the time of Nevuchadnetzer or attending Achashverosh’s feast, or perhaps for a newly created reason, altogether.